TMEM63C

protein-coding

transmembrane protein 63C

Gene summary

Enables calcium-activated cation channel activity. Involved in monoatomic cation transport. Located in lysosomal membrane and plasma membrane. Implicated in hereditary spastic paraplegia 87. Biomarker of focal segmental glomerulosclerosis. [provided by Alliance of Genome Resources, Jun 2026]

Previous symbols:

C14orf171

MANE transcript

NM_020431.4

Inheritance

ClinVar variants

P:4U:98B:8

Top phenotype

Spastic paraplegia 87, autosomal recessive

gnomAD constraint

pLI —, LoF o/e 0.23

Max pathogenic AF

—

Genomic locus

chr14:77,116,568-77,259,495

External References & Databases

Ensembl (ENSG00000165548)

Transcript & Mutation Effects

hg38 • Region Span ~142.9 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

spastic paraplegia 87, autosomal recessiveMODERATE

Inheritance Pattern: AR

Disease ID:MONDO:0031019

Submitter: G2P

spastic paraplegia 87, autosomal recessiveSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0031019

Submitter: PanelApp Australia

spastic paraplegia 87, autosomal recessiveLIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0031019

Submitter: Ambry Genetics

Clinical Genomic Database (CGD)

Spastic paraplegia 87, autosomal recessiveAR

Manifestation: Neurologic

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: 35718349

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to TMEM63C variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 96

Spastic paraplegia 87, autosomal recessiveTotal: 5

not providedTotal: 4

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_020431.4. 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			1 clinvar	6 clinvar		7
missense			93 clinvar	2 clinvar		95
nonsense	1 clinvar		2 clinvar			3
start loss						0
frameshift	3 clinvar					3
splice donor/acceptor (+/-2bp)			2 clinvar			2
Total	4	0	98	8	0	110

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 19 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_020431.4	RefSeq	NP_065164.2	22	MANE Select
ENST00000298351.5	Ensembl	ENSP00000298351.4	22	MANE Select
ENST00000554346.5	Ensembl	ENSP00000451237.1	1	Standard
ENST00000554766.5	Ensembl	ENSP00000451842.1	5	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

cation transport
ion transmembrane transport

Molecular Function

calcium activated cation channel activity

Cellular Component

plasma membrane
integral component of membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000298351
Coding exons: 22
Length: 142928
Individuals with no LoFs: 125267
Homozygous LoFs: 0
Heterozygous LoFs: 13
Defined: 125280
p: 0.0000519

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	2.07	360	489	0.737	0.0000293	5317
Missense (PolyPhen)		114	187.52	0.60794		2012
Synonymous	0.169	191	194	0.985	0.0000127	1518
Loss of Function	4.63	10	42.6	0.235	0.00000191	493

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000065	0.000063	rare
Latino/Admixed American	0.00015	0.00014	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.000056	0.000054	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.000054	0.000053	rare
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Acts as an osmosensitive calcium-permeable cation channel. {ECO:0000269|PubMed:24503647}.;

Intolerance Scores

LoFtool: 0.269
RVIS EVS: -0.71
RVIS percentile EVS: 14.71

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.261

Gene Damage Prediction

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