CFH

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

Basic information

Region (hg38): 1:196651754-196752476

Previous symbols: [ "HF", "HF1", "HF2" ]

Links

ENSG00000000971 ∙ NCBI:3075 ∙ OMIM:134370 ∙ HGNC:4883 ∙ Uniprot:P08603 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Doyne honeycomb retinal dystrophy (Supportive), mode of inheritance: AD
• dense deposit disease (Supportive), mode of inheritance: AR
• basal laminar drusen (Strong), mode of inheritance: AD
• hemolytic uremic syndrome, atypical, susceptibility to, 1 (Moderate), mode of inheritance: AD
• complement factor H deficiency (Moderate), mode of inheritance: AR
• basal laminar drusen (Limited), mode of inheritance: Unknown
• hemolytic uremic syndrome, atypical, susceptibility to, 1 (Strong), mode of inheritance: AD
• complement factor H deficiency (Strong), mode of inheritance: AR
• primary membranoproliferative glomerulonephritis (Definitive), mode of inheritance: AR
• atypical hemolytic-uremic syndrome (Definitive), mode of inheritance: Semidominant

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Hemolytic uremic syndrome, atypical; Complement factor H deficiency	AD/AR	Allergy/Immunology/Infectious; 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); In Complement factor H deficiency, antiinfectious prophylaxis and early and aggressive treatment of infections may be beneficial	Allergy/Immunology/Infectious; Hematologic; Ophthalmologic; Renal	646435; 6461667; 2950269; 2966809; 7742208; 9312129; 2966809; 9811382; 9848786; 9551389; 10577907; 10975323; 10762557; 0803850; 11170895; 14583443; 12697737; 14978182; 14583443; 16299065; 16621965; 16612335; 17018561; 18268093; 21784901

ClinVar

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

• not_provided (779 variants)
• Hemolytic_uremic_syndrome,_atypical,_susceptibility_to,_1 (312 variants)
• Age_related_macular_degeneration_4 (273 variants)
• Basal_laminar_drusen (272 variants)
• Factor_H_deficiency (264 variants)
• Inborn_genetic_diseases (99 variants)
• CFH-Related_Dense_Deposit_Disease_/_Membranoproliferative_Glomerulonephritis_Type_II (64 variants)
• not_specified (62 variants)
• Atypical_hemolytic-uremic_syndrome (39 variants)
• CFH-related_disorder (23 variants)
• Retinal_dystrophy (13 variants)
• Kidney_disorder (5 variants)
• Atypical_hemolytic-uremic_syndrome_with_I_factor_anomaly (2 variants)
• Thrombotic_microangiopathy (2 variants)
• Optic_atrophy (1 variants)
• Macular_degeneration (1 variants)
• Chronic_kidney_disease (1 variants)
• Focal_segmental_glomerulosclerosis (1 variants)
• Mesangiocapillary_glomerulonephritis,_type_II (1 variants)
• Hereditary_hemolytic_uremic_syndrome (1 variants)
• Non-immunoglobulin-mediated_membranoproliferative_glomerulonephritis (1 variants)
• Familial_Atypical_Hemolytic-Uremic_Syndrome (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CFH gene is commonly pathogenic or not. These statistics are base on transcript: NM_000000186.4. Only rare variants are included in the table.

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.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			13	176	4	193
missense	7	21	507	23	6	564
nonsense	15	15	4			34
start loss						0
frameshift	13	8	3			24
splice donor/acceptor (+/-2bp)	3	9		1		13
Total	38	53	527	200	10

Highest pathogenic variant AF is 0.00013693776

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CFH	protein_coding	protein_coding	ENST00000367429	22	95627

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.861	0.139	125728	0	16	125744	0.0000636

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.997	588	660	0.891	0.0000335	8023
Missense in Polyphen		118	208.94	0.56477		2452
Synonymous	-1.76	256	223	1.15	0.0000117	2220
Loss of Function	5.89	13	63.7	0.204	0.00000290	871

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000289	0.0000289
Ashkenazi Jewish	0.00	0.00
East Asian	0.000109	0.000109
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.0000885	0.0000879
Middle Eastern	0.000109	0.000109
South Asian	0.0000654	0.0000653
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Factor H functions as a cofactor in the inactivation of C3b by factor I and also increases the rate of dissociation of the C3bBb complex (C3 convertase) and the (C3b)NBB complex (C5 convertase) in the alternative complement pathway.
• Disease: DISEASE: Complement factor H deficiency (CFHD) [MIM:609814]: A disorder that 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 terminal complement components, indicating activation of the alternative complement pathway. It is associated with a number of renal diseases with variable clinical presentation and progression, including membranoproliferative glomerulonephritis and atypical hemolytic uremic syndrome. {ECO:0000269|PubMed:10803850, ECO:0000269|PubMed:11158219, ECO:0000269|PubMed:11170895, ECO:0000269|PubMed:11170896, ECO:0000269|PubMed:12020532, ECO:0000269|PubMed:14978182, ECO:0000269|PubMed:16612335, ECO:0000269|PubMed:9312129}. Note=The disease is caused by mutations affecting the gene represented in this entry.; 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:10577907, ECO:0000269|PubMed:10762557, ECO:0000269|PubMed:11851332, ECO:0000269|PubMed:12960213, ECO:0000269|PubMed:14583443, ECO:0000269|PubMed:14978182, ECO:0000269|PubMed:20513133, ECO:0000269|PubMed:9551389}. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry. Other genes may play a role in modifying the phenotype.; DISEASE: Macular degeneration, age-related, 4 (ARMD4) [MIM:610698]: A form of age-related macular degeneration, a multifactorial eye disease and the most common cause of irreversible vision loss in the developed world. In most patients, the disease is manifest as ophthalmoscopically visible yellowish accumulations of protein and lipid that lie beneath the retinal pigment epithelium and within an elastin-containing structure known as Bruch membrane. {ECO:0000269|PubMed:22019782}. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry.
• Pathway: Complement and coagulation cascades - Homo sapiens (human);Staphylococcus aureus infection - Homo sapiens (human);Human Complement System;Dengue-2 Interactions with Complement and Coagulation Cascades;Complement and Coagulation Cascades;Innate Immune System;Immune System;Regulation of Complement cascade;Complement cascade (Consensus)

Recessive Scores

• pRec: 0.136

Intolerance Scores

• loftool: 0.358
• rvis_EVS: 0.52
• rvis_percentile_EVS: 80.37

Haploinsufficiency Scores

• pHI: 0.100
• hipred: N
• hipred_score: 0.214
• ghis: 0.523

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.362

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Cfh
• Phenotype: homeostasis/metabolism phenotype; pigmentation phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); vision/eye phenotype; immune system phenotype; renal/urinary system phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); normal phenotype; hematopoietic system phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan)

Gene ontology

• Biological process: complement activation;complement activation, alternative pathway;viral process;regulation of complement activation
• Cellular component: extracellular region;extracellular space;extracellular exosome;blood microparticle
• Molecular function: protein binding;heparin binding;heparan sulfate proteoglycan binding