TMEM63A

protein-coding

transmembrane protein 63A

Gene summary

Enables mechanosensitive monoatomic ion channel activity. Predicted to be involved in lysosome organization and surfactant secretion. Located in bounding membrane of organelle; centriolar satellite; and plasma membrane. Implicated in hypomyelinating leukodystrophy 19. [provided by Alliance of Genome Resources, Jun 2026]

Previous symbols:

KIAA0792

MANE transcript

NM_014698.3

Inheritance

ClinVar variants

P:10U:149B:56

Top phenotype

Leukodystrophy, hypomyelinating, 19, transient infantile

gnomAD constraint

pLI —, LoF o/e 0.6

Max pathogenic AF

—

Genomic locus

chr1:225,845,536-225,882,380

External References & Databases

Ensembl (ENSG00000196187)

Transcript & Mutation Effects

hg38 • Region Span ~36.8 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

leukodystrophy, hypomyelinating, 19, transient infantileSTRONG

Inheritance Pattern: AD

Disease ID:MONDO:0032871

Submitter: Labcorp Genetics (formerly Invitae)

leukodystrophy, hypomyelinating, 19, transient infantileSTRONG

Inheritance Pattern: AD

Disease ID:MONDO:0032871

Submitter: PanelApp Australia

leukodystrophy, hypomyelinating, 19, transient infantileLIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0032871

Submitter: Ambry Genetics

leukodystrophy, hypomyelinating, 19, transient infantileSTRONG

Inheritance Pattern: AD

Disease ID:MONDO:0032871

Submitter: G2P

Clinical Genomic Database (CGD)

Leukodystrophy, hypomyelinating, 19, transient infantileAD

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: 31587869; 35718349

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to TMEM63A variants in ClinVar

7 Conditions Cataloged

Inborn genetic diseasesTotal: 119

not providedTotal: 43

Leukodystrophy, hypomyelinating, 19, transient infantileTotal: 31

not specifiedTotal: 25

TMEM63A-related disorderTotal: 13

LeukodystrophyTotal: 3

See casesTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_014698.3. 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	15 clinvar	1 clinvar	19
missense	3 clinvar	5 clinvar	125 clinvar	35 clinvar	3 clinvar	171
nonsense			3 clinvar			3
start loss			1 clinvar			1
frameshift		1 clinvar	6 clinvar	2 clinvar		9
splice donor/acceptor (+/-2bp)	1 clinvar		11 clinvar			12
Total	4	6	149	52	4	215

Highest pathogenic variant AF is 0.000006842847

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 56 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_014698.3	RefSeq	NP_055513.2	22	MANE Select
ENST00000366835.8	Ensembl	ENSP00000355800.3	22	MANE Select
ENST00000436966.1	Ensembl	ENSP00000409002.1	4	Standard
ENST00000537914.5	Ensembl	ENSP00000445237.1	2	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Neutrophil degranulation
Innate Immune System
Immune System

Biological Process

ion transmembrane transport
neutrophil degranulation

Molecular Function

nucleic acid binding
calcium activated cation channel activity

Cellular Component

lysosomal membrane
microtubule organizing center
plasma membrane
integral component of membrane
specific granule membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000366835
Coding exons: 22
Length: 36833
Individuals with no LoFs: 125532
Homozygous LoFs: 0
Heterozygous LoFs: 216
Defined: 125748
p: 0.000859

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.24	384	459	0.837	0.0000261	5273
Missense (PolyPhen)		142	173	0.8208		2052
Synonymous	0.633	179	190	0.942	0.0000114	1566
Loss of Function	2.43	26	43.2	0.601	0.00000184	519

Population LoF Frequency

Population	CAF	p-value	Status
African	0.0021	0.0021	notable
Latino/Admixed American	0.00067	0.00067	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00098	0.00098	rare
Finnish	0.000093	0.000092	rare
European (Non-Finnish)	0.00080	0.00079	rare
South Asian	0.0015	0.0014	notable
Other	0.0010	0.00098	notable

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Acts as an osmosensitive calcium-permeable cation channel. {ECO:0000250}.;

Intolerance Scores

LoFtool: 0.954
RVIS EVS: 0.58
RVIS percentile EVS: 82.34

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.347

Gene Damage Prediction

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