TMEM94

protein-coding

transmembrane protein 94, the group of MicroRNA protein coding host genes

Gene summary

Enables P-type magnesium transporter activity. Involved in magnesium ion transport from cytosol to endoplasmic reticulum. Located in nucleoplasm. Is active in endoplasmic reticulum membrane. [provided by Alliance of Genome Resources, Jun 2026]

Previous symbols:

KIAA0195

MANE transcript

NM_014738.6

Inheritance

ClinVar variants

P:29U:237B:64

Top phenotype

Intellectual developmental disorder with cardiac defects and dysmorphic facies

gnomAD constraint

pLI —, LoF o/e 0.48

Max pathogenic AF

—

Genomic locus

chr17:75,441,159-75,500,452

External References & Databases

Ensembl (ENSG00000177728)

Transcript & Mutation Effects

hg38 • Region Span ~59.3 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

intellectual developmental disorder with cardiac defects and dysmorphic faciesSUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0032672

Submitter: Orphanet

intellectual developmental disorder with cardiac defects and dysmorphic faciesDEFINITIVE

Inheritance Pattern: AR

Disease ID:MONDO:0032672

Submitter: ClinGen

The *TMEM94* gene is located on chromosome 17 at 17q25.1 and encodes transmembrane protein 94 which is involved in transport of magnesium ions into the endoplasmic reticulum . *TMEM94* was first reported in relation to autosomal recessive intellectual developmental disorder with cardiac defects and dysmorphic facies (IDDCDF) in 2018 (Stephen et al., PMID: 30526868). IDDCDF is a syndromic neurodevelopmental disorder characterized by globally impaired development with intellectual disability and speech delay, congenital cardiac malformations, and dysmorphic facial features. Individuals with this condition present with various types of structural congenital heart disease, including atrial septal defect, ventricular septal defect, and tetralogy of fallot. Ten unique variants (6 frameshift, 1 nonsense, 3 splice-site) that have been reported in 12 probands with IDDCDF in 7 publications are included in this curation (PMIDs: 30526868, 32825426, 30919572, 31607746, 32552793, 37644014, 34374989). Most probands were born from consanguineous parents and variants were identified in a homozygous state in 10 of the 12 probands. More evidence is available in the literature but the maximum score for genetic evidence (12 pts) has been reached.The mechanism of pathogenicity is reported to be loss of function. This gene-disease relationship is also supported by a mouse modelwhere the homozygous null variants fully replicated the human phenotype (PMID: 30526868). In summary, there is definitive evidence to support the relationship between *TMEM94* and autosomal recessive tntellectual developmental disorder with cardiac defects and dysmorphic facies. This has been repeatedly demonstrated in both the research and clinical diagnostic settings, and has been upheld over time. This classification was approved by the ClinGen Syndromic GCEP on the meeting date June 5th, 2024 (SOP Version 10).

intellectual developmental disorder with cardiac defects and dysmorphic faciesMODERATE

Inheritance Pattern: AR

Disease ID:MONDO:0032672

Submitter: Ambry Genetics

intellectual developmental disorder with cardiac defects and dysmorphic faciesSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0032672

Submitter: PanelApp Australia

intellectual developmental disorder with cardiac defects and dysmorphic faciesSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0032672

Submitter: G2P

Clinical Genomic Database (CGD)

Intellectual developmental disorder with cardiac defects and dysmorphic faciesAR

Manifestation: Cardiovascular; Craniofacial; Musculoskeletal; Neurologic

Intervention: Cardiovascular

Rationale: The condition can involve congenital cardiac anomalies, and awareness may allow early management

Refs: 30526868; 32825426

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to TMEM94 variants in ClinVar

8 Conditions Cataloged

Inborn genetic diseasesTotal: 187

not providedTotal: 79

not specifiedTotal: 54

Intellectual developmental disorder with cardiac defects and dysmorphic faciesTotal: 43

TMEM94-related disorderTotal: 42

Rare syndromic intellectual disabilityTotal: 2

Abnormality of the nervous systemTotal: 1

Prostate cancerTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_014738.6. 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			8 clinvar	45 clinvar	1 clinvar	54
missense			211 clinvar	16 clinvar	2 clinvar	229
nonsense	3 clinvar	5 clinvar	4 clinvar			12
start loss						0
frameshift	4 clinvar	11 clinvar	2 clinvar			17
splice donor/acceptor (+/-2bp)	2 clinvar	4 clinvar	12 clinvar			18
Total	9	20	237	61	3	330

Highest pathogenic variant AF is 0.000024784653

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 140 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_014738.6	RefSeq	NP_055553.3	31	MANE Select
ENST00000314256.12	Ensembl	ENSP00000313885.7	31	MANE Select
NM_001321148.2	RefSeq	NP_001308077.1	31	Standard
NM_001321149.2	RefSeq	NP_001308078.1	31	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Cellular Component

integral component of membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000314256
Coding exons: 31
Length: 58932
Individuals with no LoFs: 125652
Homozygous LoFs: 0
Heterozygous LoFs: 96
Defined: 125748
p: 0.000382

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	2.50	619	821	0.754	0.0000507	8839
Missense (PolyPhen)		218	335.37	0.65002		3805
Synonymous	0.654	337	353	0.956	0.0000224	2769
Loss of Function	4.07	35	72.4	0.483	0.00000381	726

Population LoF Frequency

Population	CAF	p-value	Status
African	0.0010	0.0010	notable
Latino/Admixed American	0.00044	0.00043	rare
Ashkenazi Jewish	0.00040	0.00040	rare
East Asian	0.00033	0.00033	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.00038	0.00038	rare
South Asian	0.00033	0.00033	rare
Other	0.00018	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Recessive Scores

pRec: 0.132

Intolerance Scores

RVIS EVS: -2.74
RVIS percentile EVS: 0.68

Essentials

Essential (gene trap): N