CLCC1

protein-coding

chloride channel CLIC like 1, the group of Tetraspan junctional complex superfamily

Gene summary

Enables chloride channel activity. Involved in endoplasmic reticulum calcium ion homeostasis. Located in endoplasmic reticulum membrane and mitochondria-associated endoplasmic reticulum membrane contact site. Implicated in retinitis pigmentosa 32. [provided by Alliance of Genome Resources, Jul 2025]

MANE transcript

NM_001377458.1

Inheritance

ClinVar variants

P:1U:178B:97

Top phenotype

Retinitis pigmentosa 32

gnomAD constraint

pLI —, LoF o/e 0.33

Max pathogenic AF

—

Genomic locus

chr1:108,881,885-108,963,527

External References & Databases

Ensembl (ENSG00000121940)

Transcript & Mutation Effects

hg38 • Region Span ~81.6 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

retinitis pigmentosaLIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0019200

Submitter: G2P

Clinical Genomic Database (CGD)

Retinitis pigmentosa 32AR

Manifestation: Ophthalmologic

Intervention: General

Rationale: 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

Refs: 16189710; 30157172

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to CLCC1 variants in ClinVar

5 Conditions Cataloged

not providedTotal: 285

not specifiedTotal: 77

Retinitis pigmentosa 32Total: 3

Retinal dystrophyTotal: 2

CLCC1-related conditionTotal: 2

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001377458.1. 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			3 clinvar	78 clinvar	4 clinvar	85
missense		1 clinvar	152 clinvar	11 clinvar	3 clinvar	167
nonsense			5 clinvar			5
start loss						0
frameshift			12 clinvar			12
splice donor/acceptor (+/-2bp)			6 clinvar	1 clinvar		7
Total	0	1	178	90	7	276

Highest pathogenic variant AF is 0.000023559141

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 291 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001377458.1	RefSeq	NP_001364387.1	10	MANE Select
ENST00000369969.7	Ensembl	ENSP00000358986.3	10	MANE Select
NM_001048210.3	RefSeq	NP_001041675.1	10	Standard
NM_001278202.2	RefSeq	NP_001265131.1	8	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

chloride transmembrane transport

Molecular Function

chloride channel activity

Cellular Component

nucleus
endoplasmic reticulum
Golgi apparatus
membrane
chloride channel complex

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000369971
Coding exons: 10
Length: 33982
Individuals with no LoFs: 125677
Homozygous LoFs: 0
Heterozygous LoFs: 70
Defined: 125747
p: 0.000278

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.10	245	298	0.821	0.0000155	3601
Missense (PolyPhen)		77	109.67	0.70212		1465
Synonymous	0.0567	110	111	0.993	0.00000620	1027
Loss of Function	3.29	9	27.7	0.325	0.00000133	371

Population LoF Frequency

Population	CAF	p-value	Status
African	0.0010	0.00092	notable
Latino/Admixed American	0.00024	0.00023	rare
Ashkenazi Jewish	0.00020	0.00020	rare
East Asian	0.00066	0.00065	rare
Finnish	0.000046	0.000046	rare
European (Non-Finnish)	0.00023	0.00023	rare
South Asian	0.00013	0.00013	rare
Other	0.00033	0.00033	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Seems to act as a chloride ion channel. {ECO:0000250}.;

Recessive Scores

pRec: 0.127

Intolerance Scores

LoFtool: 0.991
RVIS EVS: 1.04
RVIS percentile EVS: 91.31

Essentials

Essential (CRISPR): N
Essential (CRISPR2): S
Indispensability pred.: N
Indispensability score: 0.147

Gene Damage Prediction

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