CFHR5

complement factor H related 5, the group of Sushi domain containing|Complement system regulators and receptors

Basic information

Region (hg38): 1:196975009-197009678

Previous symbols: [ "CFHL5" ]

Links

ENSG00000134389

∙ NCBI:81494 ∙ OMIM:608593 ∙ HGNC:24668 ∙ Uniprot:Q9BXR6 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

C3 glomerulonephritis (Strong), mode of inheritance: AD
C3 glomerulonephritis (Moderate), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
CFHR5 deficiency	AD	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Renal	20800271; 22503529

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the CFHR5 gene.

not provided (105 variants)
CFH-Related Dense Deposit Disease / Membranoproliferative Glomerulonephritis Type II (72 variants)
CFHR5 deficiency (51 variants)
Inborn genetic diseases (18 variants)
not specified (15 variants)
Atypical hemolytic-uremic syndrome (14 variants)
Kidney disorder (5 variants)
Mesangiocapillary glomerulonephritis, type II (3 variants)
Chronic kidney disease (2 variants)
Variant of unknown significance (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CFHR5 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			4 clinvar	14 clinvar	3 clinvar	21
missense			56 clinvar	12 clinvar	2 clinvar	70
nonsense			5 clinvar			5
start loss			1 clinvar			1
frameshift	1 clinvar		8 clinvar			9
inframe indel			2 clinvar			2
splice donor/acceptor (+/-2bp)				1 clinvar		1
splice region ? Intron variants in splice region, excluding donor/acceptor (+/-2bp)			2	3		5
non coding ? UTR, intron and other, non coding variants			16 clinvar	2 clinvar	19 clinvar	37
Total	1	0	92	29	24

Highest pathogenic variant AF is 0.0000263

Variants in CFHR5

This is a list of pathogenic ClinVar variants found in the CFHR5 region.

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

Position	Phenotype	Significance	ClinVar
1-196977290-T-A		Benign (Jun 18, 2021)	1268818
1-196977292-GA-G		Benign (Jun 18, 2021)	1240837
1-196977318-G-A		Benign (Nov 11, 2018)	1274652
1-196977416-T-C		Benign (Nov 11, 2018)	1225260
1-196977587-CTG-C	Mesangiocapillary glomerulonephritis, type II	Uncertain significance (Jun 14, 2016)	294530
1-196977645-T-C	CFH-Related Dense Deposit Disease / Membranoproliferative Glomerulonephritis Type II • Atypical hemolytic-uremic syndrome • CFHR5 deficiency	Benign (Apr 11, 2023)	294531
1-196977665-A-G	CFHR5 deficiency	Uncertain significance (Apr 11, 2023)	1028902
1-196977678-T-A	CFHR5 deficiency	Uncertain significance (Jan 01, 2019)	982718
1-196977712-T-TG	CFHR5 deficiency	Uncertain significance (Jun 04, 2020)	1341892
1-196977715-G-A	CFH-Related Dense Deposit Disease / Membranoproliferative Glomerulonephritis Type II	Uncertain significance (Jan 12, 2018)	294532
1-196977739-T-A	CFHR5 deficiency	Benign (Jan 30, 2024)	1273904
1-196977741-C-T		Likely benign (Jun 01, 2022)	1913903
1-196977900-T-C		Benign (Jun 18, 2021)	1248903
1-196978009-C-T		Benign (Nov 11, 2018)	1277859
1-196981078-C-CAAATATTGTGCAACATTAAATATTACTTCTAGGTAGTTAAAAAAGAGAAATTTCCCTTGATTTGTCAGCTGAATTTCTGCATGCTTTTTCTAAATAAGGTGAAAAACAAAACAATTTCTTATGCAGCAATGCTATATTCAGGAAATATCTTGAGCTAAAAAATGAGCACACTATATTGAGGAAATATCTCGAGCTAAAACAGCATTCAAAGATAAAGTACATCAAATCCATAGAATGTACAATATCAAGAGTAAACCCTAATGTAAACTATGGGCTTTAATGACAATAATACTGATAGTGAAGGGGGCTATTCATGTGGCAGGGAAGAGGAAGTGGTATATAGGAAATCTCTGTACCTTCCACTCAATTTTACAGTAAAAAAACTGTAAATAAAAAATTAAGTCTAATAAAAAATATGTGTATATATAAATATATATATACACAAGAAAAAATAGAGTCAAAACATGAATATTTCACCCATTTTCTACATTGTTTTACCATATCTTGCACCATAGTGCATATGGATGTATGTGTGAGTGTCTATATAAATATATCCAGTAGTATCCTCAGTATCATTAGTATCCTTAAGGAATTGTTCCAGGACTCTTTTCACCCCCAGCAGATACCAAAATCCACAGATGCTCAAGTCTCTAAGAGAGAATGGCGTAGTATTTGCATATAACATATGCACATCCTCTCATATAATTTAAATCATCTCTAGATTATTTATAATATCTAACATAATGTAAATACTATATAAATAATTGTTATATTGTATTTTTAATTGCATTGTTTTTATTGTTTTATTATCTTTTTATTGTTTTTTCTTTTTCAGATATTTTGGACTTGCAGTATAATAAACATTTATGTATACAGCATTTACCAGAATTTAGCTCTAATTTTATCTCGGTTGAGTTGTTCTTAGTGATTTTCTTATACTCTTTAAATTATTTCCACTGAAACCACATAAACTTTGTAACCAGAAAGTAATCAGAATATTAATAAACAAAAAATCAAATTACCTACCCAACATTTTTACTGCACCAGAAAAAAAAATAGGACAGATTTTTCTGGTGGAAATACCTATGACAGTTGATGAGAATAGAAAAAGAAATAAATCTGAGAGCTGAGAACAATCCTATCACTCCTCTACTGTACACTACATAGACCAGGGAGATTTGCTACTCTTACAGTCTGCCTTCATTCTTAAATTGTTGTGTGAGGATATTGTTCTTGAAGACATTGCAGAAGAGTTCATATTTCATATCATTCCAAAATATAAATTTTATATTCATTAACAATGACCTCGTCGGTCCGGCATGGTGGTTCATGCCTGTAATCCCGGCAGTTTGGGAGGCCGAGGCGCATGGATCACCTGAGGTCAGGAGTTTGACACCAGTCTGGCCAATATGGTGAAACCTTGTCTCTACCAAAAATACAAAAAATTAGTCAGGTGTGGTGGCAGGCACCTGTAATCTCAGGTACTCAGGAGGCTGAGGCAGGAGAATCACTTGAACCCAGTGGAGGCTGCAGTGAGCCAAGATTTGCGTGATTGTACTTCAGCCTGGGCAACAAGAGTAAAACCTGAAACTCCCTCTCAAAAAAAAAAAGATCTCCTCAAATACTCTTCTATTCTTATTTAGGGATCTTTCTTCATTCCAAATTAGTACACTGGAAAGCATTTAAGCTAAAGGCATTTAAGCTGAATGAAAAACAAAACTATAAATGAGATGACTAAAATATAATCTAGTGATTCATCGATGTAGCTCTTTATTTAATTCTTCAGTTTTGTGTTATTTTTCCCAGGAACACTTTGTGATTTTCCAAAAATACACCATGGATTTCTGTATGATGAAGAAGATTATAACCCTTTTTCCCAAGTTCCTACAGGGGAAGTTTTCTATTACTCCTGTGAATATAATTTTGTGTCTCCTTCAAAATCCTTTTGGACTCGCATAACATGCACAGAAGAAGGATGGTCACCAACACCGAAGTGTCTCAGTGAGTAAATGCCCTGTTCATTAAATGGATGTCATTCAGTGAATAGAGAAGGATGTGCCGGACAAGATCATAAGGTCTTGATAATCACAAGGGCAATGACCAGAGGAGCTGGAAAAATGGGAGATGTAGTCCTCCTATTTTGAGACCCCTCCTATGAGAATCAATGAAGAATAAATATATCAACTGTCTTGCATTACCTGGAAATGCCCTACATGTTGAAATACATTAATTTTTTTAAACTGATGATTAATATATTTGACTGCTAATAGTTCTTTACTAATATTCATTCGGTAGCAGCCTGATCATAGTTTTCCTTTAAAATAAGTCATTTTATATAGATATTCTGTTTTGAATTTACCGTTCTCTTGCATATTGCGAGGTAAGGTTTGGTATTTTAACTTTTATATTTTCAATAAATCATTTATTTGGTCCTTCAAAGTGTAGCTATATTAATCCTCCAATAAATGTAGAGACCAGACTCCAATGATAACAGGTGCATTAAAAAAGAAAAACAATGGGAGAGAGAATAGATGAGGCAACAAAGGAGATAGTAATGGTCTTTCTCCTTTTGTAAGAAACATTTATGAGAATTGCGAGAAATATTTATATGAAGATATTGTTTTGGTGCTAGAAGAGTTTATAAACACAAGATTTTTATTATAAAAACCATACAGCAACAACATGAAATATTAACTTTCGTATATATATATATAGGAACAAAAAATATATTTCATCATTTATACGGTAGCATGACCCAAATTCTTTTGAAAATATTTACACATGATGTCAGTTTTCAAAGTTTTCCTTTCTTAATGAAATATTTTTAAATGCACTTTTTTTGCTACTTCCATCTTGTACATTAATCAATTTTTGTTCCTTAGGAATGTGTTCCTTTCCTTTTGTGAAAAATGGTCATTCTGAATCTTCAGGACTAATACATCTGGAAGGTGATACTGTACAAATTATTTGCAACACAGGATACAGCCTTCAAAACAATGAGAAAAACATTTCGTGTGTAGAACGGGGCTGGTCCACTCCTCCCATATGCAGCTTCACTAGTAAGCAAAATACCACTCTCTCAGTTTTGCTAATTATTTAAAGAAATAAATCTATAGTTTATAGATTAAATATAGGTTAAATATAGGTTTCACCACTACTTCTATCATTATTTATTTGATTTTCGGTTCCAATTGTGTCTAAGTAGATGTGCAATAACATAGTTTGCCTACCTATATAAATCAAATGTACGTAATAAGAAGAAATATTAGAGAAGAATACACTTTGAAGATAATCCATTAATGTAACAACTGTTTGTTGTTTATATTGTCAGGTTAGTTGACAATAAATGGTTACAAAACTGAGGTATTAAAGTGCAAATTAGTCCAATTACAGTTAAAATGTCTTATAAGGAAGTTTTTAATATTTATCTTTATTTAAATTAATATGCTTGAGTCAATAAATCATTTTCTAAGTTGTAAAAAGTCCATACTTCTGAGAGGTATGTGTATTTGTGAGCGGCTTAGAATTTGGAAAACGATTCTTTTGGAAGCCTGTGGTATAAATGATGGCACCTCACAGTCCTGTGTGAACTCTTGTAATTCTTCATCTTTATAGCTCTTCAGTAATTGTTCTTTGCCCAGCCCAATGCGATTCCATCCTATGCTTACACACCTCAGTATTCAACCAAACACTCAAGGAAACTTCCATAGTCTTTCTCTTCATACCACTTTCTCTCTGCTACTATGTCCAGTAACTTCTGGCCACCATAGTCACCAAGACTGACCTTACTAGTCTCAACTAAAGAAGACCACTGAGTTCTTCCTGGGTTCTCCCTCCTTGCACAGTCTAGAAAAGGCTTCCCAATAAACAGCTGGGCTTTCATTGACTTTGCTTTATTATTTTGAAGTATTGAGGGTTTTTTCCTTTTTTCAGTCATCACAGTTCTGTACTGGGTGATTTCCAGCATTCTGAAAATAAATTTTGTAAAATTTTCTAAATTTTTTTTCAGTGGGATGCTATGTTGATAGCAGCTACTCCATCCTATCAAGAAATAGAATCTGTGGTAGGTTTTTCAAAAGATGTTATGTTATCAAATATTATTCCACATCTTCAACTCTTAATTTAAACCTCTAGAGCCAGGCACAGTGATGTGCACCTGTAGTCCCCGCCACTGGCAAGGCTGAAATAGGAGTTCAAAGCTTCAGTGAGTTATGACTGCACCAGTGCACTCCAACCCAGGCAACAAAGTGAGACCCTTCCCCACTAGAAAAACAAAACAAAGTAAAGCAAAATGAAATTTAAACCTCTAGAAATGGAGTCTTTTTAAAACAGCTGGAACTGCGATAGTTTTTCAGTAAACAGTTACGTCATGGTCTCTTTCAATTACAAGGGGTTAAAACATTATTAACATTTGCAAAAAAAAAAAATAACAAATGTTACTAACACTAGAAAATTCCAGTGATTGAAAAGGGTTCAAAATGTATAGGCTTCAGTTATGGTATAAATATTTCCATGCTTTCTCTTATCCATACCTGTTCATGTCATGAACAAGCTCTCTTCATTTTGAGAGATGATGGCTATTGTCAGACCAACAATTATATTTTAGAAGCTTGACAAATTAAGTTTGGCCAGCGTAACCCATACAAGCTGGCTCTGTGTACAGTCTGTAAGATTTTGTTAGTCTTTGAACAATTCGGTTGCTTTGTGACACAAAAAATATCCCAGGCTTAACTCATGTTTCCACTGCCCCAGAACTAGAATCAGCCATACCTCCAATAAGTCCTGGTTCCATTTAGTGGGCAATGACATTTAGAAACTAAGTTGTCAAAATAAACTTGTTTCAAAATTTAGCACATTTTATTTAATCAGAAAAAGCACATATCTTATTGTTCAAGTTCTCAGAATATTGCTGCCTTTCCCTTTCTGCCCGTTGCTTATTCCAAAAGCACAAGACAACATATTGAGGTTATCAGAGTAGATGGACAGATGGACCAAGTCAGAGTCTCCAAAGTGAAAGAATTCAGCAGAACACTCTGTGCCTAAGGTTGAATGGTAGCTCACGAACACTGTGGAAAGTTAATAAAGTTTCAGGGCAACTAGACTCCTAATGATAGCGGCACAGTCTGTTTATTCATGTAAGGTAACATCTTGCAAGTTATGGTAATCCATGTTGCAGGGATTAGTATGGCGTCATCTCTGGGGGCCGTTATTCCATTTACAACACCATGCAATAACCATATATGAATAAAGCAGCTGGAAAACCCTACATTGGCCAAGATCGATTATTTTCTTTTTATATATATATATATACTTTAAGTTCTAGGGTACATGCGCACAACATGCAGGTTTGTTACATAGGTATACATGTGTCATATTGGTTTGCTGCACCCATTAACTCGTGATTTACATTATGTATTTTGCCTAATGCTACCCCTCCCCTACCTCCCACCCTACAACAGGCCCCAGTGTGTGATGTTCCCCACCCTGTGTCCAAGTGTTCCCATTGTTCAATTCCCACCTGTGAGTGAGAACATGCAGTGTTTGGTTTTCTGTCCTTGTGATAGTTTTCTCAGAATGATGGTTTCCAGGTTCATCCATGACCCTGCAAAGGACAAGAACTCATCCTTTTTTATGGCTGCATAGTATTCCATGGTGTATGTGTGCCGCATTTTCTTAATCCAGTCTATCACTTACGGACATTTGGGCTAGTTCCAGGTCTTTGCTATTGTGAATACTGCCACAATAAACCTATGTGTGCATGTATCTTTATAGCAGCATGATTTATAATCTTATGGGTATATACCCAGTAATGAGATCACTGGGTCAAATGGTATTTCTGGTTCTAGATCCTTGAGGAATTGCCACACTGTCTACCACAATGGTTGAACTAGTTTACACTCCCAACAACAGTGTAAAAGAGTTCCTATTTCTCCACATCCTCTCTAGAATCTGTTGTTCCCTGACTTTTTAATGATCGCCATTCTAACTGGTGTGAGATGGTATCTCATTGTGGTTTTGATTTGCATTTCTCTGATGACCAGTGATGATCAGCATTTTTTCATGTGTCTGTTGGCTGAATAAATGTCTTCTTTTAAGAAGTGTCTGTTCATATCCTTTGCCCACTTTTTGATGGGGTTTTTTCTTGTAGATTTGTTTAAGTTCTTTGTAGATTCTGGCTATCAGCCCTTTATCAGATGGGTAGATTGCAAAGATTTTCTCCCATTCTGTACGTTGCCTGTTCACTCTGATGGTAGTTTCTTTTGCTGTGCAGAAGCTCTTTAGTT	CFHR5 deficiency	Pathogenic (Sep 04, 2010)	37236
1-196982740-A-G		Benign (Jun 19, 2021)	1222004
1-196982870-T-C		Likely benign (Nov 06, 2023)	2992054
1-196982885-GA-G		Uncertain significance (Apr 01, 2022)	2066804
1-196982888-C-T		Uncertain significance (May 12, 2022)	2682707
1-196982897-A-C	Inborn genetic diseases	Uncertain significance (Jun 23, 2023)	2597054
1-196982900-T-A		Uncertain significance (Nov 17, 2023)	2980214
1-196982902-C-T	CFH-Related Dense Deposit Disease / Membranoproliferative Glomerulonephritis Type II	Uncertain significance (Mar 30, 2018)	874580
1-196982916-T-A	Inborn genetic diseases	Uncertain significance (Oct 20, 2021)	3143834
1-196982938-G-T	Inborn genetic diseases	Uncertain significance (Aug 16, 2022)	2397702
1-196982941-T-C	Inborn genetic diseases	Uncertain significance (Mar 01, 2024)	3143823

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CFHR5	protein_coding	protein_coding	ENST00000256785	10	32138

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
2.11e-32	2.01e-7	125379	0	364	125743	0.00145

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.903	349	305	1.15	0.0000150	3702
Missense in Polyphen		115	108.61	1.0589		1281
Synonymous	-1.91	130	105	1.24	0.00000542	1046
Loss of Function	-2.16	41	28.5	1.44	0.00000140	361

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00149	0.00149
Ashkenazi Jewish	0.0000992	0.0000992
East Asian	0.000326	0.000326
Finnish	0.000185	0.000185
European (Non-Finnish)	0.000114	0.000114
Middle Eastern	0.000326	0.000326
South Asian	0.00947	0.00948
Other	0.00212	0.00212

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. {ECO:0000269|PubMed:23487775}.;
Disease: DISEASE: CFHR5 deficiency (CFHR5D) [MIM:614809]: A progressive disease characterized by glomerulonephritis, hematuria, renal failure, end-stage renal disease, subendothelial and mesangial glomerular C3 deposits, mesangial matrix expansion, increased glomerular cellularity, and segmental capillary wall thickening. Hematuria may become apparent after respiratory infections. {ECO:0000269|PubMed:20800271, ECO:0000269|PubMed:22503529}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
Pathway: Innate Immune System;Immune System;Regulation of Complement cascade;Complement cascade (Consensus)

Intolerance Scores

loftool: 0.613
rvis_EVS: 0.18
rvis_percentile_EVS: 66.24

Haploinsufficiency Scores

pHI: 0.0403
hipred: N
hipred_score: 0.112
ghis

Essentials

essential_gene_CRISPR: N
essential_gene_CRISPR2: N
essential_gene_gene_trap: N
gene_indispensability_pred: E
gene_indispensability_score: 0.588

Gene Damage Prediction

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

Gene ontology

Biological process: complement activation, alternative pathway;regulation of complement activation;negative regulation of protein binding;positive regulation of cytolysis
Cellular component: extracellular region;protein-containing complex
Molecular function: protein binding;protein homodimerization activity;protein heterodimerization activity