CFHR4

complement factor H related 4, the group of Complement system regulators and receptors|Sushi domain containing

Basic information

Region (hg38): 1:196888013-196918795

Previous symbols: [ "CFHL4" ]

Links

ENSG00000134365 ∙ NCBI:10877 ∙ OMIM:605337 ∙ HGNC:16979 ∙ Uniprot:Q92496 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

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	19861685; 20301541
Deletions related to hemolytic-uremic syndrome involve a contiguous deletion with CFHR3 or CFHR4

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the CFHR4 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CFHR4 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				5	4	9
missense			41	7	8	56
nonsense			1			1
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)			1			1
splice region						0
non coding				1	11	12
Total	0	0	43	13	23

Variants in CFHR4

This is a list of pathogenic ClinVar variants found in the CFHR4 region.

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

Position	Type	Phenotype	Significance	ClinVar
1-196888191-C-A			Uncertain significance (Apr 03, 2024)
1-196888194-G-T			Uncertain significance (Oct 26, 2022)
1-196902421-T-C		not specified	Benign (May 14, 2019)
1-196902427-C-T		not specified	Uncertain significance (Feb 28, 2023)
1-196902462-T-C		not specified • Kidney disorder	Likely benign (Jun 10, 2020)
1-196902477-C-T		Kidney disorder	Uncertain significance (May 01, 2017)
1-196902478-G-A		not specified	Uncertain significance (Aug 13, 2021)
1-196902487-A-T		Atypical hemolytic-uremic syndrome	Likely benign (Jan 05, 2021)
1-196902518-C-T		not specified	Benign (May 14, 2019)
1-196902544-C-T		not specified	Conflicting classifications of pathogenicity (Nov 12, 2021)
1-196902563-G-A		not specified	Uncertain significance (Apr 13, 2023)
1-196902587-T-C		not specified • Atypical hemolytic-uremic syndrome	Benign/Likely benign (Aug 01, 2023)
1-196902602-G-A		not specified	Benign (May 14, 2019)
1-196905128-G-A		not specified	Benign (May 14, 2019)
1-196905165-C-G		not specified	Uncertain significance (Dec 28, 2022)
1-196905199-T-A		not specified	Benign (May 14, 2019)
1-196905222-C-A		not specified	Uncertain significance (Nov 12, 2021)
1-196905226-G-T			Benign (Jun 09, 2021)
1-196905264-G-T		not specified	Uncertain significance (Feb 17, 2024)
1-196906850-T-C		not specified	Likely benign (Nov 02, 2023)
1-196906866-T-C		not specified	Uncertain significance (May 01, 2024)
1-196906897-C-T			Uncertain significance (Nov 07, 2022)
1-196906982-C-T			Likely benign (Mar 30, 2018)
1-196907017-C-A		not specified	Uncertain significance (Jan 26, 2023)
1-196907017-C-T		not specified	Uncertain significance (Aug 12, 2021)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CFHR4	protein_coding	protein_coding	ENST00000367416	10	68732

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
2.38e-18	0.00763	125250	6	485	125741	0.00195

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-1.17	357	300	1.19	0.0000143	3730
Missense in Polyphen		113	97.267	1.1618		1171
Synonymous	-2.25	138	108	1.28	0.00000552	1030
Loss of Function	0.265	28	29.6	0.947	0.00000134	389

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00136	0.00132
Ashkenazi Jewish	0.00	0.00
East Asian	0.00525	0.00518
Finnish	0.0000929	0.0000924
European (Non-Finnish)	0.000316	0.000308
Middle Eastern	0.00525	0.00518
South Asian	0.0116	0.0106
Other	0.00136	0.00130

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Involved in complement regulation. Can associate with lipoproteins and may play a role in lipid metabolism.
• Pathway: Human Complement System;Innate Immune System;Immune System;Regulation of Complement cascade;Complement cascade (Consensus)

Recessive Scores

• pRec: 0.135

Haploinsufficiency Scores

• pHI: 0.0688
• hipred: N
• hipred_score: 0.112

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.539

Gene Damage Prediction

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

Gene ontology

• Biological process: lipid transport;regulation of complement activation
• Cellular component: extracellular region
• Molecular function: lipid transporter activity