CFHR1

complement factor H related 1, the group of Sushi domain containing|Complement system regulators and receptors

Basic information

Region (hg38): 1:196819730-196837159

Previous symbols: [ "HFL1", "CFHL1", "CFHR1P", "HFL2", "CFHL1P" ]

Links

ENSG00000244414 ∙ NCBI:3078 ∙ OMIM:134371 ∙ HGNC:4888 ∙ Uniprot:Q03591 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• hemolytic uremic syndrome, atypical, susceptibility to, 1 (Limited), mode of inheritance: AD
• dense deposit disease (Supportive), mode of inheritance: AR
• hemolytic uremic syndrome, atypical, susceptibility to, 1 (Limited), mode of inheritance: Unknown
• age related macular degeneration 1 (Limited), mode of inheritance: Unknown

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Hemolytic-uremic syndrome, atypical, susceptibility to	AD/AR/Digenic	Hematologic; Pharmacogenomic; Renal	In Hemolytic-uremic syndrome, the choice of specific treatment modalities (eg, danazol, plasma exchange, plasma therapy), as well as decision to perform renal transplant, may be dictated by genetic diagnosis, and certain agents/precipitating factors should be avoided (eg, certain medications)	Hematologic; Renal	98489; 17367211; 18006700; 19435718; 20301541
Deletions related to hemolytic-uremic syndrome involve a contiguous deletion with CFHR1

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the CFHR1 gene.

• not provided (56 variants)
• Inborn genetic diseases (13 variants)
• not specified (11 variants)
• Chronic kidney disease (3 variants)
• Kidney disorder (1 variants)
• Age related macular degeneration 1;Hemolytic uremic syndrome, atypical, susceptibility to, 1 (1 variants)
• Hemolytic uremic syndrome, atypical, susceptibility to, 1 (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CFHR1 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				2	5	7
missense		2	18	1	5	26
nonsense			1			1
start loss						0
frameshift			1			1
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding			2	4	32	38
Total	0	2	22	7	42

Variants in CFHR1

This is a list of pathogenic ClinVar variants found in the CFHR1 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
1-196819862-TG-T		Hemolytic uremic syndrome, atypical, susceptibility to, 1;Age related macular degeneration 1	Conflicting classifications of pathogenicity (Dec 01, 2022)
1-196820031-C-G			Benign (Jul 09, 2018)
1-196820070-A-G			Benign (Jul 09, 2018)
1-196825296-G-C			Benign (Jul 09, 2018)
1-196825316-G-A			Benign (Oct 26, 2018)
1-196825319-G-GT			Benign (Jul 09, 2018)
1-196825389-C-T			Benign (Jul 09, 2018)
1-196825463-T-C			Uncertain significance (Feb 10, 2022)
1-196825548-C-T			Uncertain significance (Aug 20, 2021)
1-196825551-G-T		not specified	Benign (May 14, 2019)
1-196825557-A-G		not specified	Uncertain significance (Feb 17, 2024)
1-196825576-A-C		not specified	Uncertain significance (Aug 08, 2022)
1-196825613-A-C		not specified	Likely benign (Jan 26, 2018)
1-196825619-G-T		not specified	Uncertain significance (Nov 29, 2023)
1-196825620-A-G		not specified	Uncertain significance (Jul 26, 2022)
1-196825626-A-G		not specified	Uncertain significance (Jun 21, 2022)
1-196825635-A-G			Uncertain significance (Dec 22, 2020)
1-196825737-G-A			Benign (Jul 09, 2018)
1-196825779-G-C			Benign (Jul 09, 2018)
1-196825884-G-A			Benign (Jul 09, 2018)
1-196825888-T-G			Benign (Jul 09, 2018)
1-196825962-G-A			Benign (Oct 07, 2019)
1-196826611-C-T			Benign (Jul 09, 2018)
1-196826631-C-G			Benign (Jul 09, 2018)
1-196826714-C-T			Benign (Jul 09, 2018)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CFHR1	protein_coding	protein_coding	ENST00000320493	6	12433

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
2.63e-8	0.164	118387	138	241	118766	0.00160

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.328	184	172	1.07	0.00000890	2104
Missense in Polyphen		67	60.487	1.1077		693
Synonymous	-0.751	65	57.7	1.13	0.00000269	624
Loss of Function	0.166	12	12.6	0.950	5.31e-7	181

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0297	0.0210
Ashkenazi Jewish	0.000131	0.000107
East Asian	0.000383	0.000383
Finnish	0.00109	0.000994
European (Non-Finnish)	0.000382	0.000285
Middle Eastern	0.000383	0.000383
South Asian	0.000406	0.000295
Other	0.00120	0.00103

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Involved in complement regulation. The dimerized forms have avidity for tissue-bound complement fragments and efficiently compete with the physiological complement inhibitor CFH. Can associate with lipoproteins and may play a role in lipid metabolism. {ECO:0000269|PubMed:23487775}.
• Disease: DISEASE: Hemolytic uremic syndrome atypical 1 (AHUS1) [MIM:235400]: An atypical form of hemolytic uremic syndrome. It is a complex genetic disease characterized by microangiopathic hemolytic anemia, thrombocytopenia, renal failure and absence of episodes of enterocolitis and diarrhea. In contrast to typical hemolytic uremic syndrome, atypical forms have a poorer prognosis, with higher death rates and frequent progression to end-stage renal disease. {ECO:0000269|PubMed:17367211}. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry. A deletion encompassing CFHR1 and CFHR3 is associated with an increased risk of atypical hemolytic uremic syndrome, likely due to a defective regulation of complement activation (PubMed:17367211). Some patients carrying the deletion have serum anti-CFH autoantibodies (PubMed:18006700). {ECO:0000269|PubMed:17367211, ECO:0000269|PubMed:18006700}.
• Pathway: Innate Immune System;Immune System;Regulation of Complement cascade;Complement cascade (Consensus)

Intolerance Scores

• loftool: 0.828
• rvis_EVS: 0.77
• rvis_percentile_EVS: 87.06

Haploinsufficiency Scores

• hipred: N
• hipred_score: 0.195
• ghis: 0.426

Essentials

• essential_gene_CRISPR: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.0920

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Cfhr1

Gene ontology

• Biological process: complement activation;regulation of complement activation;negative regulation of protein binding;positive regulation of cytolysis
• Cellular component: extracellular region;extracellular space;protein-containing complex;blood microparticle
• Molecular function: protein binding;protein homodimerization activity;protein heterodimerization activity