TMEM63B

protein-coding

transmembrane protein 63B

Gene summary

Enables calcium-activated cation channel activity; mechanosensitive monoatomic cation channel activity; and phospholipid scramblase activity. Predicted to be involved in several processes, including drinking behavior; intestinal stem cell homeostasis; and surfactant secretion. Located in actin cytoskeleton and bounding membrane of organelle. Is active in plasma membrane. Implicated in developmental and epileptic encephalopathy and developmental and epileptic encephalopathy 118. [provided by Alliance of Genome Resources, Jun 2026]

Previous symbols:

C6orf110

MANE transcript

NM_018426.3

Inheritance

ClinVar variants

P:12U:110B:18

Top phenotype

genetic developmental and epileptic encephalopathy

gnomAD constraint

pLI —, LoF o/e 0.07

Max pathogenic AF

—

Genomic locus

chr6:44,126,914-44,155,519

External References & Databases

Ensembl (ENSG00000137216)

Transcript & Mutation Effects

hg38 • Region Span ~28.6 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

TMEM63B-related developmental and epileptic encephalopathy with anemiaMODERATE

Inheritance Pattern: AD

Disease ID:MONDO:0800503

Submitter: G2P

genetic developmental and epileptic encephalopathySTRONG

Inheritance Pattern: AD

Disease ID:MONDO:0100062

Submitter: PanelApp Australia

complex neurodevelopmental disorderSTRONG

Inheritance Pattern: AD

Disease ID:MONDO:0100038

Submitter: Ambry Genetics

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to TMEM63B variants in ClinVar

9 Conditions Cataloged

Inborn genetic diseasesTotal: 69

not providedTotal: 58

Developmental and epileptic encephalopathy 118Total: 5

LUNG-BRAIN DEVELOPMENTAL DISORDERTotal: 5

TMEM63B-related conditionTotal: 3

not specifiedTotal: 2

Rare epilepsyTotal: 1

TMEM63B-related Neurodevelopmental disorderTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_018426.3. 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	11 clinvar		14
missense	3 clinvar	4 clinvar	93 clinvar	7 clinvar		107
nonsense	1 clinvar		1 clinvar			2
start loss						0
frameshift	3 clinvar		4 clinvar			7
splice donor/acceptor (+/-2bp)	1 clinvar		9 clinvar			10
Total	8	4	110	18	0	140

Highest pathogenic variant AF is 0.000006573412

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 79 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_018426.3	RefSeq	NP_060896.1	23	MANE Select
ENST00000323267.11	Ensembl	ENSP00000327154.6	23	MANE Select
NM_001318792.1	RefSeq	NP_001305721.1	23	Standard
ENST00000259746.13	Ensembl	ENSP00000259746.9	23	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Fibroblast growth factor-1

Biological Process

ion transmembrane transport

Molecular Function

calcium activated cation channel activity

Cellular Component

plasma membrane
actin cytoskeleton
integral component of membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000259746
Coding exons: 23
Length: 28606
Individuals with no LoFs: 125735
Homozygous LoFs: 0
Heterozygous LoFs: 8
Defined: 125743
p: 0.0000318

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	4.22	243	511	0.475	0.0000309	5448
Missense (PolyPhen)		56	193.94	0.28874		2065
Synonymous	-1.14	234	213	1.10	0.0000136	1635
Loss of Function	5.88	3	46.1	0.0651	0.00000231	525

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0.000046	0.000046	rare
European (Non-Finnish)	0.000054	0.000053	rare
South Asian	0.000033	0.000033	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

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

Intolerance Scores

LoFtool: 0.0706
RVIS EVS: -1.11
RVIS percentile EVS: 6.78

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Indispensability pred.: E
Indispensability score: 0.519

Gene Damage Prediction

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