TMEM147

protein-coding

transmembrane protein 147

Gene summary

Enables ribosome binding activity. Involved in multi-pass transmembrane protein insertion into ER membrane and protein localization to nuclear inner membrane. Located in nuclear membrane. Part of multi-pass translocon complex. Is active in endoplasmic reticulum membrane. [provided by Alliance of Genome Resources, Jul 2025]

MANE transcript

NM_032635.4

Inheritance

ClinVar variants

P:16U:39B:4

Top phenotype

Neurodevelopmental disorder with facial dysmorphism, absent language, and pseudo-Pelger-Huet anomaly

gnomAD constraint

pLI —, LoF o/e 0.59

Max pathogenic AF

—

Genomic locus

chr19:35,545,600-35,547,526

External References & Databases

Ensembl (ENSG00000105677)

Transcript & Mutation Effects

hg38 • Region Span ~1.9 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

neurodevelopmental disorder with facial dysmorphism, absent language, and pseudo-pelger-huet anomalySTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0859298

Submitter: PanelApp Australia

neurodevelopmental disorder with facial dysmorphism, absent language, and pseudo-pelger-huet anomalySTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0859298

Submitter: Labcorp Genetics (formerly Invitae)

complex neurodevelopmental disorderMODERATE

Inheritance Pattern: AR

Disease ID:MONDO:0100038

Submitter: Ambry Genetics

neurodevelopmental disorder with facial dysmorphism, absent language, and pseudo-pelger-huet anomalySTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0859298

Submitter: G2P

Clinical Genomic Database (CGD)

Neurodevelopmental disorder with facial dysmorphism, absent language, and pseudo-Pelger-Huet anomalyAR

Manifestation: Craniofacial; Hematologic; Musculoskeletal; 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: 36044892

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to TMEM147 variants in ClinVar

10 Conditions Cataloged

Inborn genetic diseasesTotal: 33

Neurodevelopmental disorder with facial dysmorphism, absent language, and pseudo-pelger-huet anomalyTotal: 19

not providedTotal: 9

TMEM147-related disorderTotal: 2

Motor delayTotal: 1

Poor speechTotal: 1

Abnormal facial shapeTotal: 1

Severe intellectual disabilityTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_032635.4. 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				3 clinvar		3
missense		3 clinvar	34 clinvar	1 clinvar		38
nonsense	3 clinvar		1 clinvar			4
start loss						0
frameshift	4 clinvar	1 clinvar	1 clinvar			6
splice donor/acceptor (+/-2bp)	3 clinvar	2 clinvar	3 clinvar			8
Total	10	6	39	4	0	59

Highest pathogenic variant AF is 0.00007129616

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 32 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_032635.4	RefSeq	NP_116024.1	7	MANE Select
ENST00000222284.10	Ensembl	ENSP00000222284.4	7	MANE Select
NM_001242597.2	RefSeq	NP_001229526.1	5	Standard
NM_001242598.2	RefSeq	NP_001229527.1	5	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Molecular Function

protein binding

Cellular Component

endoplasmic reticulum membrane
integral component of membrane
protein-containing complex

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000222284
Coding exons: 7
Length: 1932
Individuals with no LoFs: 125724
Homozygous LoFs: 0
Heterozygous LoFs: 24
Defined: 125748
p: 0.0000954

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.485	121	137	0.883	0.00000796	1465
Missense (PolyPhen)		37	50.098	0.73855		568
Synonymous	0.325	51	54.0	0.944	0.00000328	440
Loss of Function	1.38	8	13.5	0.594	6.61e-7	141

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00012	0.00012	rare
Latino/Admixed American	0.000029	0.000029	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00022	0.00022	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.000080	0.000079	rare
South Asian	0.00023	0.00023	rare
Other	0.00016	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Recessive Scores

pRec: 0.140

Intolerance Scores

LoFtool: 0.676
RVIS EVS: -0.3
RVIS percentile EVS: 32.62

Essentials

Essential (CRISPR): E
Essential (CRISPR2): S
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.653

Gene Damage Prediction

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