CFHR2

protein-coding

complement factor H related 2, the group of Complement system regulators and receptors|Sushi domain containing

Gene summary

This gene belongs to a family of complement factor H-related genes (CFHR), which are clustered together with complement factor H gene on chromosome 1, and are involved in regulation of complement. Mutations in CFHR genes have been associated with dense deposit disease and atypical haemolytic-uraemic syndrome. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Aug 2015]

Previous symbols:

HFL3
CFHL2

MANE transcript

NM_005666.4

Inheritance

—

ClinVar variants

U:35B:23

Top phenotype

Atypical hemolytic-uremic syndrome

gnomAD constraint

pLI —, LoF o/e 1.19

Max pathogenic AF

—

Genomic locus

chr1:196,943,738-196,959,622

External References & Databases

Ensembl (ENSG00000080910)

Transcript & Mutation Effects

hg38 • Region Span ~15.9 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to CFHR2 variants in ClinVar

7 Conditions Cataloged

not specifiedTotal: 47

not providedTotal: 32

Atypical hemolytic-uremic syndromeTotal: 3

High myopiaTotal: 1

Primary ciliary dyskinesiaTotal: 1

Complement 3 glomerulopathyTotal: 1

Kidney disorderTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_005666.4. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous				5 clinvar	1 clinvar	6
missense			33 clinvar	13 clinvar		46
nonsense				1 clinvar	1 clinvar	2
start loss						0
frameshift			1 clinvar	2 clinvar		3
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	0	0	35	21	2	58

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 116 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_005666.4	RefSeq	NP_005657.1	5	MANE Select
ENST00000367415.8	Ensembl	ENSP00000356385.4	5	MANE Select
NM_001312672.1	RefSeq	NP_001299601.1	3	Standard
NM_001410924.1	RefSeq	NP_001397853.1	4	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Human Complement System
Innate Immune System
Immune System
Regulation of Complement cascade
Complement cascade

Biological Process

regulation of complement activation
negative regulation of protein binding
positive regulation of cytolysis

Molecular Function

protein binding
protein homodimerization activity
protein heterodimerization activity

Cellular Component

extracellular region
protein-containing complex

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000367415
Coding exons: 5
Length: 139459
Individuals with no LoFs: 125302
Homozygous LoFs: 4
Heterozygous LoFs: 428
Defined: 125734
p: 0.00172

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.902	160	131	1.22	0.00000607	1734
Missense (PolyPhen)		65	52.265	1.2437		643
Synonymous	-2.21	64	45.1	1.42	0.00000211	502
Loss of Function	-0.535	11	9.24	1.19	3.88e-7	133

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000062	0.000062	rare
Latino/Admixed American	0.000087	0.000087	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.019	0.019	notable
Finnish	0	0.0	absent
European (Non-Finnish)	0.000035	0.000035	rare
South Asian	0.0024	0.0024	notable
Other	0.0011	0.0011	notable

dbNSFP Gene Annotations

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}.;

Recessive Scores

pRec: 0.0924

Intolerance Scores

LoFtool: 0.687
RVIS EVS: 1.35
RVIS percentile EVS: 94.31

Essentials

Essential (CRISPR): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.0767

Gene Damage Prediction

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