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Primary immunodeficiency or monogenic inflammatory bowel disease v9.18 CFH Ida Ertmanska changed review comment from: PMID: 36211394 Gouda et al., 2022
Egyptian cohort of 40 patients with LN, lupus nephritis (23) or PIGN, post-infectious glomerulonephritis (17), tested for genetic variants in CFH and CD46 genes. VUS CFH:p.F614S variant was found in 28 (70%) of patients: 17 (74%) of LN patients, and 11 (65%) of PIGN patients. 3 Pathogenic CFH mutations were detected in a heterozygous state in LN patients: c.514C>T (p.Q172*), c.2103G>A (p.W701*), and c.3288G>A (p.W1096*).

PMID: 35084692 Shears et al., 2022
Forty patients, median age 19 (range 3–62) years, were identified with terminal complement deficiencies. 2 White European patients had CFH variants and meningococcal infections and septicemia; 1 patient had non-meningococcal sepsis. Both were homozygous for CFH c.2T>C, p.Met1? variant (related?).

PMID: 32064578 Brodszki et al., 2020
"Complement deficiencies account for ~5% of PIDs." <30 patients reported with CFH variants according to the lit review.

PMID: 31440263 Sissy et al., 2019
13 patients reported with 7 different homozygous CFH variants and Factor H deficiency (primarily resulting in severe or multiple infections—mainly meningococcal infections—or severe autoimmune diseases). However, in this cohort, all 13 patients with CFH variants presented with kidney disease and no recurrent infections.

PMID: 14978182 Dragon-Durey et al., 2004
Reported are 16 FH-deficient patients. Among six patients with homozygous deficiency, four presented with membranoproliferative glomerulonephritis, and two with atypical hemolytic uremic syndrome (HUS). The ten other patients had heterozygous FH deficiency and developed atypical HUS. No mention of recurring infections in these patients - authors pose that previously reported susceptibility to meningococcal disease is secondary to acquired C3 or C5-C9 deficiencies.

Functional:
PMID: 12091909 Pickering et al., 2002 - mouse Cfh knockout caused membranoproliferative glomerulonephritis, seen at 8 months old.

CFH is associated with AD,AR Complement factor H deficiency, OMIM:609814 and AD, AR {Hemolytic uremic syndrome, atypical, susceptibility to, 1}, OMIM:235400, among others (OMIM accessed 22nd Jun 2026). The association between CFH and semidominant atypical hemolytic-uremic syndrome is Definitive in ClinGen (Complement-Mediated Kidney Diseases GCEP, July 2023); CFH-related AR C3 glomerulonephritis is also Definitive (Complement-Mediated Kidney Diseases GCEP, Feb 2024).; to: PMID: 36211394 Gouda et al., 2022
Egyptian cohort of 40 patients with LN, lupus nephritis (23) or PIGN, post-infectious glomerulonephritis (17), tested for genetic variants in CFH and CD46 genes. VUS CFH:p.F614S variant was found in 28 (70%) of patients: 17 (74%) of LN patients, and 11 (65%) of PIGN patients. 3 Pathogenic CFH mutations were detected in a heterozygous state in LN patients: c.514C>T (p.Q172*), c.2103G>A (p.W701*), and c.3288G>A (p.W1096*).

PMID: 35084692 Shears et al., 2022
Forty patients, median age 19 (range 3–62) years, were identified with terminal complement deficiencies. 2 White European patients had CFH variants and meningococcal infections and septicemia; 1 of these patients also had non-meningococcal sepsis. Both were homozygous for CFH c.2T>C, p.Met1? variant (related?).

PMID: 32064578 Brodszki et al., 2020
"Complement deficiencies account for ~5% of PIDs." <30 patients reported with CFH variants according to the lit review.

PMID: 31440263 Sissy et al., 2019
13 patients reported with 7 different homozygous CFH variants and Factor H deficiency (primarily resulting in severe or multiple infections—mainly meningococcal infections—or severe autoimmune diseases). However, in this cohort, all 13 patients with CFH variants presented with kidney disease and no recurrent infections.

PMID: 14978182 Dragon-Durey et al., 2004
Reported are 16 FH-deficient patients. Among six patients with homozygous deficiency, four presented with membranoproliferative glomerulonephritis, and two with atypical hemolytic uremic syndrome (HUS). The ten other patients had heterozygous FH deficiency and developed atypical HUS. No mention of recurring infections in these patients - authors pose that previously reported susceptibility to meningococcal disease is secondary to acquired C3 or C5-C9 deficiencies.

Functional:
PMID: 12091909 Pickering et al., 2002 - mouse Cfh knockout caused membranoproliferative glomerulonephritis, seen at 8 months old.

CFH is associated with AD,AR Complement factor H deficiency, OMIM:609814 and AD, AR {Hemolytic uremic syndrome, atypical, susceptibility to, 1}, OMIM:235400, among others (OMIM accessed 22nd Jun 2026). The association between CFH and semidominant atypical hemolytic-uremic syndrome is Definitive in ClinGen (Complement-Mediated Kidney Diseases GCEP, July 2023); CFH-related AR C3 glomerulonephritis is also Definitive (Complement-Mediated Kidney Diseases GCEP, Feb 2024).
Primary immunodeficiency or monogenic inflammatory bowel disease v9.18 CD46 Ida Ertmanska edited their review of gene: CD46: Changed rating: AMBER; Changed publications to: 14566051, 16621965, 16762990, 29644059, 33238263, 40983966; Changed phenotypes to: {Hemolytic uremic syndrome, atypical, susceptibility to, 2}, OMIM:612922; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Primary immunodeficiency or monogenic inflammatory bowel disease v9.18 CD46 Ida Ertmanska changed review comment from: PMID: 33238263 Bamhraz et al., 2020
Saudi Arabian aHUS cohort.
Patient 1 homozygous for CD46: c.736T>A (p.Phe246Ile) variant, as well as het for CFI c.540A>G (p.Glu180Glu) - both labelled VUS. Disease onset at 10yrs, complete recovery after eculizumab treatment.
Patient 5 - homozygous for CD46: c.769 C>A (p.Cys 256*) - LP, as well as heterozygous for CFI c.803 C>T (p.Ser268Leu) variant (LB). Disease onset at 2.5yrs, developed into ESRD and required a post-kidney transplant.
Patient 7 - homozygous for CD46: c.350-351dup AC (p.Glu11ThfsX17) - LP. Disease onset at 21 months. Patient responded to plasma therapy leading to full recovery.

PMID: 29644059 Khandelwal et al., 2018
Cohort of Indian children with aHUS.
Sibling pairs 2–3 and 7–8 with familial disease showed a homozygous c.286 + 2T > G splice-site mutation; in both families, the parents were consanguineous. Patient 9 had a homozygous c.104G > A, p.Cys35Tyr; his affected sibling had died before genetic evaluation. 3 unrelated families total.; to: BIALLELIC CASES:
PMID: 40983966 Hu et al., 2025
Case of a 27-year-old Chinese male diagnosed with atypical Hemolytic Uremic Syndrome (aHUS) at the age of 8, who has experienced seven relapses over a span of 19 years. He was homozygous for a mutation in CD46: c.1127+2T>A (WES). CD46 mRNA and protein expression in the patient's peripheral blood were significantly reduced. Other modifier mutations may affect penetrance here.

PMID: 33238263 Bamhraz et al., 2020
Saudi Arabian aHUS cohort.
Patient 1 homozygous for CD46: c.736T>A (p.Phe246Ile) variant, as well as het for CFI c.540A>G (p.Glu180Glu) - both labelled VUS. Disease onset at 10yrs, complete recovery after eculizumab treatment.
Patient 5 - homozygous for CD46: c.769 C>A (p.Cys 256*) - LP, as well as heterozygous for CFI c.803 C>T (p.Ser268Leu) variant (LB). Disease onset at 2.5yrs, developed into ESRD and required a post-kidney transplant.
Patient 7 - homozygous for CD46: c.350-351dup AC (p.Glu11ThfsX17) - LP. Disease onset at 21 months. Patient responded to plasma therapy leading to full recovery.

PMID: 29644059 Khandelwal et al., 2018
Cohort of Indian children with aHUS.
Sibling pairs 2–3 and 7–8 with familial disease showed a homozygous c.286 + 2T > G splice-site mutation; in both families, the parents were consanguineous. Patient 9 had a homozygous c.104G > A, p.Cys35Tyr; his affected sibling had died before genetic evaluation. 3 unrelated families total.

PMID: 16762990 Fremeaux-Bacchi et al., 2006
3 homozygous aHUS patients (onset at 2, 5, and 27yrs).
Patient 1 - born with Pierre Robin sequence, presented with common variable immunodeficiency. Developed aHUS at 27yrs. Homozygous for CD46 R25X. MFI on granulocytes for CD46 expression was 0.
Patient 2 was homozygous for CD46 Y214X (no CD46 expression on granulocytes; Patient 3 homozygous for IVS2+2T>G - CD46 MFI level was 46 (normal range 600-1400). No mention of immunodeficiency in Patients 2 & 3.

PMID: 16621965 Caprioli et al., 2006
Family 099 - Sardinian origin, 2 individuals homozygous for CD46 IVS1-1G > C, and 1 heterozygous affected member (4 het carriers unaffected). The homozygous sibs developed aHUS early (before age 4 yrs); adult onset seen in heterozygous family members.
Family 024 - 2 comp het sibs CD46 variants c.218C>T, p.R25Stop & c.147G>A, p.C1Y - showed almost no MCP staining by FACS. Parents were carriers of 1 mutation each, unaffected.

PMID: 14566051 Richards et al., 2003
Family 3 - recessive aHUS, CD46 c.822T>C, p.Ser206Pro. Same mutation caused aHUS in Family 2 in a heterozygous state. Demonstrated that het patients had protein expression reduced by 50%, and it was absent in homozygotes.
Primary immunodeficiency or monogenic inflammatory bowel disease v9.15 CD46 Ida Ertmanska reviewed gene: CD46: Rating: ; Mode of pathogenicity: None; Publications: 29644059, 33238263; Phenotypes: ; Mode of inheritance: None
Primary immunodeficiency or monogenic inflammatory bowel disease v9.9 CFH Ida Ertmanska changed review comment from: PMID: 36211394 Gouda et al., 2022
Egyptian cohort of 40 patients with LN, lupus nephritis (23) or PIGN, post-infectious glomerulonephritis (17), tested for genetic variants in CFH and CD46 genes. VUS CFH:p.F614S variant was found in 28 (70%) of patients: 17 (74%) of LN patients, and 11 (65%) of PIGN patients. 3 Pathogenic CFH mutations were detected in a heterozygous state in LN patients: c.514C>T (p.Q172*), c.2103G>A (p.W701*), and c.3288G>A (p.W1096*).

PMID: 35084692 Shears et al., 2022
Forty patients, median age 19 (range 3–62) years, were identified with terminal complement deficiencies. 2 White European patients had CFH variants and meningococcal infections and septicemia; 1 patient had non-meningococcal sepsis. Both were homozygous for CFH c.2T>C, p.Met1? variant (related?).

PMID: 32064578 Brodszki et al., 2020
"Complement deficiencies account for ~5% of PIDs." <30 patients reported with CFH variants according to the lit review.

PMID: 31440263 Sissy et al., 2019
13 patients reported with 7 different homozygous CFH variants and Factor H deficiency (primarily resulting in severe or multiple infections—mainly meningococcal infections—or severe autoimmune diseases). However, in this cohort, all 13 patients with CFH variants presented with kidney disease and no recurrent infections.

PMID: 14978182 Dragon-Durey et al., 2004
Reported are 16 FH-deficient patients. Among six patients with homozygous deficiency, four presented with membranoproliferative glomerulonephritis, and two with atypical hemolytic uremic syndrome (HUS). The ten other patients had heterozygous FH deficiency and developed atypical HUS.

CFH is associated with AD,AR Complement factor H deficiency, OMIM:609814 and AD, AR {Hemolytic uremic syndrome, atypical, susceptibility to, 1}, OMIM:235400, among others (OMIM accessed 22nd Jun 2026). The association between CFH and semidominant atypical hemolytic-uremic syndrome is Definitive in ClinGen (Complement-Mediated Kidney Diseases GCEP, July 2023); CFH-related AR C3 glomerulonephritis is also Definitive (Complement-Mediated Kidney Diseases GCEP, Feb 2024).; to: PMID: 36211394 Gouda et al., 2022
Egyptian cohort of 40 patients with LN, lupus nephritis (23) or PIGN, post-infectious glomerulonephritis (17), tested for genetic variants in CFH and CD46 genes. VUS CFH:p.F614S variant was found in 28 (70%) of patients: 17 (74%) of LN patients, and 11 (65%) of PIGN patients. 3 Pathogenic CFH mutations were detected in a heterozygous state in LN patients: c.514C>T (p.Q172*), c.2103G>A (p.W701*), and c.3288G>A (p.W1096*).

PMID: 35084692 Shears et al., 2022
Forty patients, median age 19 (range 3–62) years, were identified with terminal complement deficiencies. 2 White European patients had CFH variants and meningococcal infections and septicemia; 1 patient had non-meningococcal sepsis. Both were homozygous for CFH c.2T>C, p.Met1? variant (related?).

PMID: 32064578 Brodszki et al., 2020
"Complement deficiencies account for ~5% of PIDs." <30 patients reported with CFH variants according to the lit review.

PMID: 31440263 Sissy et al., 2019
13 patients reported with 7 different homozygous CFH variants and Factor H deficiency (primarily resulting in severe or multiple infections—mainly meningococcal infections—or severe autoimmune diseases). However, in this cohort, all 13 patients with CFH variants presented with kidney disease and no recurrent infections.

PMID: 14978182 Dragon-Durey et al., 2004
Reported are 16 FH-deficient patients. Among six patients with homozygous deficiency, four presented with membranoproliferative glomerulonephritis, and two with atypical hemolytic uremic syndrome (HUS). The ten other patients had heterozygous FH deficiency and developed atypical HUS. No mention of recurring infections in these patients - authors pose that previously reported susceptibility to meningococcal disease is secondary to acquired C3 or C5-C9 deficiencies.

Functional:
PMID: 12091909 Pickering et al., 2002 - mouse Cfh knockout caused membranoproliferative glomerulonephritis, seen at 8 months old.

CFH is associated with AD,AR Complement factor H deficiency, OMIM:609814 and AD, AR {Hemolytic uremic syndrome, atypical, susceptibility to, 1}, OMIM:235400, among others (OMIM accessed 22nd Jun 2026). The association between CFH and semidominant atypical hemolytic-uremic syndrome is Definitive in ClinGen (Complement-Mediated Kidney Diseases GCEP, July 2023); CFH-related AR C3 glomerulonephritis is also Definitive (Complement-Mediated Kidney Diseases GCEP, Feb 2024).
Primary immunodeficiency or monogenic inflammatory bowel disease v1.94 CD46 Louise Daugherty commented on gene: CD46: Gene rating submitted by Kimberly Gilmour and Austen Worth on behalf of London North GLH for the GMS Immunology specialist test group. As discussed with the GMS Immunology Specialist Test Group during webex call 28th March 2019 and confirmed in follow up email 6th September the Specialist Test Group all agreed there is enough evidence to rate this gene Green.
Primary immunodeficiency or monogenic inflammatory bowel disease v1.94 CD46 Louise Daugherty commented on gene: CD46: Gene rating submitted by Tracy Briggs, David Gokhale and Abigal Rousseau on behalf of North West GLH for the GMS Immunology specialist test group. As discussed with the GMS Immunology Specialist Test Group during webex call 28th March 2019 and confirmed in follow up email on 20th June the Specialist Test Group all agreed there is enough evidence to rate this gene Green.
Primary immunodeficiency or monogenic inflammatory bowel disease v1.94 CD46 Kimberly Gilmour reviewed gene: CD46: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Primary immunodeficiency or monogenic inflammatory bowel disease v1.94 CD46 Tracy Briggs reviewed gene: CD46: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Primary immunodeficiency or monogenic inflammatory bowel disease v1.60 CD46 Louise Daugherty Source NHS GMS was added to CD46.
Primary immunodeficiency or monogenic inflammatory bowel disease v1.59 CD46 Louise Daugherty Source North West GLH was added to CD46.
Primary immunodeficiency or monogenic inflammatory bowel disease v1.58 CD46 Louise Daugherty Source London North GLH was added to CD46.
Primary immunodeficiency or monogenic inflammatory bowel disease CD46 Louise Daugherty commented on gene: CD46
Primary immunodeficiency or monogenic inflammatory bowel disease CD46 Louise Daugherty marked gene: CD46 as ready
Primary immunodeficiency or monogenic inflammatory bowel disease CD46 Louise Daugherty classified CD46 as Green List (high evidence)
Primary immunodeficiency or monogenic inflammatory bowel disease CD46 Louise Daugherty edited their review of gene: CD46
Primary immunodeficiency or monogenic inflammatory bowel disease CD46 Sophie Hambleton reviewed gene: CD46
Primary immunodeficiency or monogenic inflammatory bowel disease CD46 Louise Daugherty commented on CD46
Primary immunodeficiency or monogenic inflammatory bowel disease CD46 Louise Daugherty commented on CD46
Primary immunodeficiency or monogenic inflammatory bowel disease CD46 Louise Daugherty commented on CD46
Primary immunodeficiency or monogenic inflammatory bowel disease CD46 Louise Daugherty reviewed CD46
Primary immunodeficiency or monogenic inflammatory bowel disease CD46 Louise Daugherty Added gene to panel
Primary immunodeficiency or monogenic inflammatory bowel disease CD46 Louise Daugherty Added gene to panel