CFHR3

complement factor H related 3, the group of Sushi domain containing|Complement system regulators and receptors

Basic information

Region (hg38): 1:196774813-196795407

Previous symbols: [ "CFHL3" ]

Links

ENSG00000116785 ∙ NCBI:10878 ∙ OMIM:605336 ∙ HGNC:16980 ∙ Uniprot:Q02985 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• hemolytic uremic syndrome, atypical, susceptibility to, 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	16998489; 17367211; 18006700; 20694013; 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 CFHR3 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CFHR3 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				10	3	13
missense			22	8	4	34
nonsense			2			2
start loss						0
frameshift			3			3
inframe indel						0
splice donor/acceptor (+/-2bp)			1			1
splice region			1	2		3
non coding				3	9	12
Total	0	0	28	21	16

Variants in CFHR3

This is a list of pathogenic ClinVar variants found in the CFHR3 region.

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

Position	Type	Phenotype	Significance	ClinVar
1-196774834-C-A			Benign (Nov 10, 2018)
1-196774896-C-T			Benign (Dec 31, 2019)
1-196774900-T-C		not specified	Uncertain significance (Aug 17, 2022)
1-196774913-G-A			Likely benign (Jun 20, 2018)
1-196774914-A-T		not specified	Uncertain significance (May 30, 2024)
1-196774939-G-C		Atypical hemolytic-uremic syndrome • not specified	Benign (Jul 01, 2020)
1-196774949-G-A		CFHR3-related disorder	Likely benign (Oct 31, 2019)
1-196774952-A-G			Likely benign (Dec 31, 2019)
1-196779204-T-G		Age related macular degeneration 1;Hemolytic uremic syndrome, atypical, susceptibility to, 1 • Kidney disorder	Benign/Likely benign (Oct 27, 2021)
1-196779209-G-T		not specified	Uncertain significance (Nov 25, 2022)
1-196779218-C-T			Uncertain significance (Nov 23, 2022)
1-196779219-G-A			Uncertain significance (Jan 27, 2022)
1-196779219-G-T		not specified	Uncertain significance (Jun 17, 2024)
1-196779260-T-C			Uncertain significance (Nov 15, 2022)
1-196779264-A-G		not specified	Uncertain significance (Dec 14, 2023)
1-196779305-G-A		not specified	Uncertain significance (May 24, 2024)
1-196779312-T-C		not specified	Uncertain significance (Dec 27, 2023)
1-196779338-C-T		not specified	Uncertain significance (Nov 08, 2021)
1-196779546-A-G			Benign (Nov 10, 2018)
1-196779842-A-G			Benign (Oct 10, 2018)
1-196779843-T-C		CFHR3-related disorder	Likely benign (Oct 12, 2022)
1-196779849-A-G			Likely benign (May 02, 2018)
1-196779897-C-A			Uncertain significance (Aug 20, 2021)
1-196779897-C-T			Benign/Likely benign (Nov 01, 2023)
1-196779898-G-C		Kidney disorder	Uncertain significance (Feb 22, 2018)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CFHR3	protein_coding	protein_coding	ENST00000367425	6	19279

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.72e-11	0.0318	118757	138	535	119430	0.00282

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.000941	172	172	1.00	0.00000831	2112
Missense in Polyphen		87	77.832	1.1178		984
Synonymous	-0.369	65	61.3	1.06	0.00000314	600
Loss of Function	-0.227	16	15.0	1.06	7.11e-7	196

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00143	0.00103
Ashkenazi Jewish	0.00	0.00
East Asian	0.00127	0.00104
Finnish	0.00217	0.00193
European (Non-Finnish)	0.00393	0.00317
Middle Eastern	0.00127	0.00104
South Asian	0.0110	0.00826
Other	0.00426	0.00360

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Might be involved in complement regulation.
• Pathway: Innate Immune System;Immune System;Regulation of Complement cascade;Complement cascade (Consensus)

Intolerance Scores

• loftool: 0.531
• rvis_EVS: 1.73
• rvis_percentile_EVS: 96.56

Haploinsufficiency Scores

• pHI: 0.0890
• hipred: N
• hipred_score: 0.112

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.530

Gene Damage Prediction

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

Gene ontology

• Cellular component: extracellular space;extracellular exosome;blood microparticle