Primary immunodeficiency or monogenic inflammatory bowel disease

Gene: CFH

I don't know

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).

Created: 22 Jun 2026, 2:42 p.m. | Last Modified: 26 Jun 2026, 11:18 a.m.

Panel Version: 9.18

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Complement factor H deficiency, OMIM:609814; {Hemolytic uremic syndrome, atypical, susceptibility to, 1}, OMIM:235400

Publications

• 12091909
• 14978182
• 31440263
• 32064578
• 35084692
• 36211394

Green List (high evidence)

agree with green gene

Created: 17 Sep 2019, 3:18 p.m. | Last Modified: 17 Sep 2019, 3:18 p.m.

Panel Version: 1.94

Green List (high evidence)

YES- this is covered on our targeted exome

Created: 17 Sep 2019, 3:18 p.m. | Last Modified: 17 Sep 2019, 3:18 p.m.

Panel Version: 1.94

Green List (high evidence)

Green List (high evidence)

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.

Created: 17 Sep 2019, 3:18 p.m. | Last Modified: 17 Sep 2019, 3:18 p.m.

Panel Version: 1.94

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.

Created: 17 Sep 2019, 3:18 p.m. | Last Modified: 17 Sep 2019, 3:18 p.m.

Panel Version: 1.94

OriginaI Metadata from IUIS classification table (February, 2018) downloaded 20180614. IUIS Genetic defect (original gene symbol in IUIS download): CFH .PanelApp HGNC gene symbol check: CFH . IUIS Disease: Factor H deficiency . IUIS Inheritance: AR or AD .T cells: Normal, .B cells: N/A, .IUIS Other affected cells: N/A. IUIS Associated features: Infections, disseminated neisserial infections, atypical Hemolytic-uremic syndrome, preeclampsia, dense deposit disease. IUIS Major category: Complement Deficiencies. IUIS Subcategory: N/A

Created: 2 Jul 2018, 10:35 a.m.

Comment on phenotypes: Homozygous factor H deficiency is rare, reported cases with Factor H deficiency classically presents with MPGN or other renal disease.It has also been associated with most inherited cases of HUS. Factor H deficiency has also been associated with increased susceptibility to infection in general (PMID:16499568)

Created: 8 Jun 2018, 4:43 p.m.

Comment on list classification: changed from Amber to Green

Created: 8 Jun 2018, 4:14 p.m.

Comment on publications: added publications to support immune dysfunction, more than three unrelated cases with Factor H deficiency caused by variants in CFH

Created: 8 Jun 2018, 4:11 p.m.

from OMIM : Complement factor H deficiency (CFHD) can manifest as several different phenotypes, including asymptomatic, recurrent bacterial infections, and renal failure. Laboratory features usually include decreased serum levels of factor H, complement component C3 and a decrease in other alternative pathway components, indicating activation of the alternative complement pathway. Homozygotes and heterozygotes may show increased susceptibility to meningococcal infections. In addition, a number of renal diseases have been associated with factor H defect or deficiency, including atypical hemolytic-uremic syndrome (aHUS), membranoproliferative glomerulonephritis type II (MPGN II), and nonspecific hematuria or nephritis.

Created: 8 Jun 2018, 3:58 p.m.

Comment on phenotypes: removed phenotypes not relevant to this panel
{Hemolytic uremic syndrome, atypical, susceptibility to, 1}, 235400;{Macular degeneration, age-related, 4}, 610698;Basal laminar drusen, 126700

Created: 8 Jun 2018, 3:46 p.m.

This gene was present in the original PanelApp PID panel dataset (review in April 2018) rated as Red. The gene is present in the external expert immunodeficiency diagnostic gene list(s) GOSH or GRID. In this combined PID panel, this gene has been rated as AMBER and needs further curational review to assess pertinence prior to v1.

Created: 20 Apr 2018, 12:25 p.m.

Original metadata downloaded from ESID Registry. ESID_Gene_original: Factor H, PanelApp HGNC gene symbol check: CFH, ESID classification: Main_category/ Sub_category/ PID_Diagnosis Complement deficiencies / Complement deficiency / Complement factor H deficiency

Created: 17 Apr 2018, 12:29 p.m.

Original metadata supplied by GRID. GRID Gene Symbol HGNC PanelApp check: CFH, GRID_Gene_Symbol: CFH, GRID_Transcript_ENS_Community submitted: ENST00000367429, GRID_Transcript_RefSeq: NM_000186.3, GRID_Transcript_ENS_used_on_Production: ENST00000367429

Created: 17 Apr 2018, 12:12 p.m.