C1RL

protein-coding

complement C1r subcomponent like, the group of Sushi domain containing

Gene summary

Predicted to enable serine-type endopeptidase activity. Predicted to be involved in zymogen activation. Located in extracellular exosome and obsolete extracellular space. [provided by Alliance of Genome Resources, Jun 2026]

MANE transcript

NM_016546.4

Inheritance

—

ClinVar variants

U:72B:12

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.74

Max pathogenic AF

—

Genomic locus

chr12:7,089,587-7,109,238

External References & Databases

Ensembl (ENSG00000139178)

Transcript & Mutation Effects

hg38 • Region Span ~19.7 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 C1RL variants in ClinVar

1 Conditions Cataloged

not specifiedTotal: 78

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_016546.4. 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						0
missense			71 clinvar	12 clinvar		83
nonsense			1 clinvar			1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	72	12	0	84

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 41 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_016546.4	RefSeq	NP_057630.2	6	MANE Select
ENST00000266542.9	Ensembl	ENSP00000266542.4	6	MANE Select
NM_001297640.2	RefSeq	NP_001284569.1	5	Standard
NM_001297642.2	RefSeq	NP_001284571.1	6	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

complement activation, classical pathway
zymogen activation
innate immune response

Molecular Function

serine-type endopeptidase activity

Cellular Component

extracellular space
extracellular exosome

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000266542
Coding exons: 6
Length: 19687
Individuals with no LoFs: 125701
Homozygous LoFs: 0
Heterozygous LoFs: 45
Defined: 125746
p: 0.000179

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.902	243	286	0.850	0.0000158	3169
Missense (PolyPhen)		65	67.41	0.96424		756
Synonymous	0.281	120	124	0.968	0.00000791	967
Loss of Function	1.05	14	18.9	0.739	8.10e-7	209

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00025	0.00025	rare
Latino/Admixed American	0.000087	0.000087	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00038	0.00038	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.000081	0.000079	rare
South Asian	0.00071	0.00069	rare
Other	0.00016	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Mediates the proteolytic cleavage of HP/haptoglobin in the endoplasmic reticulum. {ECO:0000269|PubMed:15358180, ECO:0000269|PubMed:15385675, ECO:0000269|PubMed:15527420}.;

Recessive Scores

pRec: 0.104

Intolerance Scores

LoFtool: 0.262
RVIS EVS: -0.2
RVIS percentile EVS: 39.11

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.539

Gene Damage Prediction

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