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Primary immunodeficiency or monogenic inflammatory bowel disease v4.83 TFRC Achchuthan Shanmugasundram changed review comment from: Comment on list classification: Although there were eight unrelated families reported with immunodeficiency (MIM #616740), they all harboured the same homozygous variant p.Tyr20His. Functional studies and mouse model provide supporting evidence in associating TFRC with green rating in this panel.

Although this variant is found in a homozygous region that is identified between two different families from different geographic regions in PMID:26642240, the segregation of this variant with the phenotype supports this gene-disease association. Hence, this gene can be promoted to green rating in the next GMS review.; to: Comment on list classification: Although there were eight unrelated families reported with immunodeficiency (MIM #616740), they all harboured the same homozygous variant p.Tyr20His. Functional studies and mouse model provide supporting evidence in associating TFRC with green rating in this panel.

Although this variant is found in a homozygous region that is shared between two different families from different geographic regions reported in PMID:26642240, the segregation of this variant with the phenotype supports this gene-disease association. Hence, this gene can be promoted to green rating in the next GMS review.

The 'founder-effect' tag has also been added to highlight this.
Primary immunodeficiency or monogenic inflammatory bowel disease v4.83 TFRC Achchuthan Shanmugasundram changed review comment from: Comment on list classification: Although there were eight unrelated families reported with immunodeficiency, they all harboured the same homozygous variant p.Tyr20His. Functional studies and mouse model provide supporting evidence in associating TFRC with green rating in this panel.

Although this variant is found in a homozygous region that is identified between two different families from different geographic regions in PMID:26642240, the segregation of this variant with the phenotype supports this gene-disease association. Hence, this gene can be promoted to green rating in the next GMS review.; to: Comment on list classification: Although there were eight unrelated families reported with immunodeficiency (MIM #616740), they all harboured the same homozygous variant p.Tyr20His. Functional studies and mouse model provide supporting evidence in associating TFRC with green rating in this panel.

Although this variant is found in a homozygous region that is identified between two different families from different geographic regions in PMID:26642240, the segregation of this variant with the phenotype supports this gene-disease association. Hence, this gene can be promoted to green rating in the next GMS review.
Primary immunodeficiency or monogenic inflammatory bowel disease v4.83 TFRC Achchuthan Shanmugasundram Phenotypes for gene: TFRC were changed from Recurrent infections, neutropenia, thrombocytopenia; Recurrent infections, thrombocytopenia; Immunodeficiencies affecting cellular and humoral immunity; Immunodeficiency 46, 616740; T cells: normal number, poor proliferation; B cells: normal number, low memory B cells; recurrent infections, neutorpaenia; thrombocytopaenia to Immunodeficiency 46, OMIM:616740
Primary immunodeficiency or monogenic inflammatory bowel disease v4.82 TFRC Achchuthan Shanmugasundram Publications for gene: TFRC were set to 32086639; 26642240; 32048120
Primary immunodeficiency or monogenic inflammatory bowel disease v4.81 TFRC Achchuthan Shanmugasundram Classified gene: TFRC as Amber List (moderate evidence)
Primary immunodeficiency or monogenic inflammatory bowel disease v4.81 TFRC Achchuthan Shanmugasundram Added comment: Comment on list classification: Although there were eight unrelated families reported with immunodeficiency, they all harboured the same homozygous variant p.Tyr20His. Functional studies and mouse model provide supporting evidence in associating TFRC with green rating in this panel.

Although this variant is found in a homozygous region that is identified between two different families from different geographic regions in PMID:26642240, the segregation of this variant with the phenotype supports this gene-disease association. Hence, this gene can be promoted to green rating in the next GMS review.
Primary immunodeficiency or monogenic inflammatory bowel disease v4.81 TFRC Achchuthan Shanmugasundram Gene: tfrc has been classified as Amber List (Moderate Evidence).
Primary immunodeficiency or monogenic inflammatory bowel disease v4.80 TFRC Achchuthan Shanmugasundram changed review comment from: PMID:26642240 - c.58T>C (p.Tyr20His) variant was present in homozygous state in patients A1 and A2 from the family from Kuwait and unaffected father had the same variant in heterozygous state. This variant segregated perfectly with the combined immunodeficiency phenotype in 34 available family members and was absent from multiple variant databases and 731 genotyped controls.

The same homozygous variant was found in patient B1 from Western Saudi Arabian family, while this variant was present in heterozygous state in his parents and his sister. Although the families were from different geographic regions and not known to be related, Patient B1 shares a homozygous haplotype with the five genotyped patients from Family A across a 3.3 Mb interval at chromosome 3q29-ter that includes TFRC, suggesting identical by descent inheritance of the mutation from an unknown common ancestor.

Functional evidence shows that this substitution disrupts the TfR1 internalization motif, resulting in defective receptor endocytosis and markedly increased TfR1 expression on the cell surface. Iron citrate rescued the lymphocyte defects, and expression of wild-type but not mutant TfR1 rescued impaired transferrin uptake in patient-derived fibroblasts.

In addition, transgenic mice homozygous for the human TFRC mutation Y20H were viable and recapitulated the human phenotype.


PMID:32851577 - Eight patients from six different tribes of Arab descent were identified with the same previously reported homozygous variant (p.Tyr20His) and they all presented with recurrent sinopulmonary infections, chronic diarrhea, and failure to thrive in early life.

This gene has been associated with relevant phenotypes in both OMIM (MIM #616740) and Gene2Phenotype (with 'limited' rating in the DD panel).; to: PMID:26642240 - c.58T>C (p.Tyr20His) variant was present in homozygous state in patients A1 and A2 from the family from Kuwait and unaffected father had the same variant in heterozygous state. This variant segregated perfectly with the immunodeficiency phenotype in 34 available family members and was absent from multiple variant databases and 731 genotyped controls.

The same homozygous variant was found in patient B1 from Western Saudi Arabian family, while this variant was present in heterozygous state in his parents and his sister. Although the families were from different geographic regions and not known to be related, Patient B1 shares a homozygous haplotype with the five genotyped patients from Family A across a 3.3 Mb interval at chromosome 3q29-ter that includes TFRC, suggesting identical by descent inheritance of the mutation from an unknown common ancestor.

Functional evidence shows that this substitution disrupts the TfR1 internalization motif, resulting in defective receptor endocytosis and markedly increased TfR1 expression on the cell surface. Iron citrate rescued the lymphocyte defects, and expression of wild-type but not mutant TfR1 rescued impaired transferrin uptake in patient-derived fibroblasts.

In addition, transgenic mice homozygous for the human TFRC mutation Y20H were viable and recapitulated the human phenotype.


PMID:32851577 - Eight patients from six different tribes of Arab descent were identified with the same previously reported homozygous variant (p.Tyr20His) and they all presented with recurrent sinopulmonary infections, chronic diarrhea, and failure to thrive in early life.

This gene has been associated with relevant phenotypes in both OMIM (MIM #616740) and Gene2Phenotype (with 'limited' rating in the DD panel).
Primary immunodeficiency or monogenic inflammatory bowel disease v4.80 TFRC Achchuthan Shanmugasundram Tag founder-effect tag was added to gene: TFRC.
Primary immunodeficiency or monogenic inflammatory bowel disease v4.80 TFRC Achchuthan Shanmugasundram Tag Q4_23_promote_green tag was added to gene: TFRC.
Tag Q4_23_NHS_review tag was added to gene: TFRC.
Primary immunodeficiency or monogenic inflammatory bowel disease v4.80 TFRC Achchuthan Shanmugasundram reviewed gene: TFRC: Rating: GREEN; Mode of pathogenicity: None; Publications: 26642240, 32851577; Phenotypes: Immunodeficiency 46, OMIM:616740; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Primary immunodeficiency or monogenic inflammatory bowel disease v4.41 TFRC Hannah Knight reviewed gene: TFRC: Rating: GREEN; Mode of pathogenicity: None; Publications: 32851577; Phenotypes: Immunodeficiency 46; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Primary immunodeficiency or monogenic inflammatory bowel disease v2.209 TFRC Eleanor Williams Source Other was added to TFRC.
Publications for gene TFRC were updated from 32048120; 32086639; 26642240 to 32086639; 26642240; 32048120
Primary immunodeficiency or monogenic inflammatory bowel disease v2.208 TFRC Eleanor Williams reviewed gene: TFRC: Rating: ; Mode of pathogenicity: ; Publications: 26642240; Phenotypes: ; Mode of inheritance:
Primary immunodeficiency or monogenic inflammatory bowel disease v2.81 TFRC Ivone Leong Classified gene: TFRC as Amber List (moderate evidence)
Primary immunodeficiency or monogenic inflammatory bowel disease v2.81 TFRC Ivone Leong Added comment: Comment on list classification: Promoted from Red to Amber based on expert review and evidence.
Primary immunodeficiency or monogenic inflammatory bowel disease v2.81 TFRC Ivone Leong Gene: tfrc has been classified as Amber List (Moderate Evidence).
Primary immunodeficiency or monogenic inflammatory bowel disease v2.80 TFRC Ivone Leong Phenotypes for gene: TFRC were changed from Recurrent infections, neutropenia, thrombocytopenia; Recurrent infections, thrombocytopenia; Immunodeficiencies affecting cellular and humoral immunity to Recurrent infections, neutropenia, thrombocytopenia; Recurrent infections, thrombocytopenia; Immunodeficiencies affecting cellular and humoral immunity; Immunodeficiency 46, 616740; T cells: normal number, poor proliferation; B cells: normal number, low memory B cells; recurrent infections, neutorpaenia; thrombocytopaenia
Primary immunodeficiency or monogenic inflammatory bowel disease v2.79 TFRC Ivone Leong Publications for gene: TFRC were set to 32048120; 32086639
Primary immunodeficiency or monogenic inflammatory bowel disease v2.51 TFRC Zornitza Stark reviewed gene: TFRC: Rating: AMBER; Mode of pathogenicity: None; Publications: 26642240; Phenotypes: Immunodeficiency 46, MIM# 616740, T cells: normal number, poor proliferation, B cells: normal number, low memory B cells, recurrent infections, neutorpaenia, thrombocytopaenia; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Primary immunodeficiency or monogenic inflammatory bowel disease v2.34 TFRC Louise Daugherty Source IUIS Classification December 2019 was added to TFRC.
Mode of inheritance for gene TFRC was changed from to BIALLELIC, autosomal or pseudoautosomal
Added phenotypes Recurrent infections, thrombocytopenia; Immunodeficiencies affecting cellular and humoral immunity for gene: TFRC
Publications for gene TFRC were updated from to 32048120; 32086639
Primary immunodeficiency or monogenic inflammatory bowel disease TFRC Louise Daugherty commented on gene: TFRC
Primary immunodeficiency or monogenic inflammatory bowel disease TFRC Louise Daugherty reviewed gene: TFRC
Primary immunodeficiency or monogenic inflammatory bowel disease TFRC Louise Daugherty Added gene to panel