THUMPD1

protein-coding

THUMP domain containing 1

Gene summary

Enables RNA binding activity. Predicted to be involved in tRNA modification. Predicted to be located in nucleoplasm. [provided by Alliance of Genome Resources, Jul 2025]

MANE transcript

NM_017736.5

Inheritance

ClinVar variants

P:9U:60B:2

Top phenotype

Neurodevelopmental disorder with speech delay and variable ocular anomalies

gnomAD constraint

pLI —, LoF o/e 1.06

Max pathogenic AF

—

Genomic locus

chr16:20,702,816-20,742,084

External References & Databases

Ensembl (ENSG00000066654)

Transcript & Mutation Effects

hg38 • Region Span ~39.3 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

neurodevelopmental disorder with speech delay and variable ocular anomaliesSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0859272

Submitter: Labcorp Genetics (formerly Invitae)

neurodevelopmental disorder with speech delay and variable ocular anomaliesMODERATE

Inheritance Pattern: AR

Disease ID:MONDO:0859272

Submitter: G2P

neurodevelopmental disorder with speech delay and variable ocular anomaliesSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0859272

Submitter: PanelApp Australia

neurodevelopmental disorder with speech delay and variable ocular anomaliesMODERATE

Inheritance Pattern: AR

Disease ID:MONDO:0859272

Submitter: Ambry Genetics

Clinical Genomic Database (CGD)

Neurodevelopmental disorder with speech delay and variable ocular anomaliesAR

Manifestation: Craniofacial; Dental; Musculoskeletal; Neurologic; Ophthalmologic

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: 30237576; 35196516

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to THUMPD1 variants in ClinVar

4 Conditions Cataloged

Inborn genetic diseasesTotal: 56

Neurodevelopmental disorder with speech delay and variable ocular anomaliesTotal: 9

Neurodevelopmental disorderTotal: 9

not providedTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_017736.5. 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			1
missense	1 clinvar		56 clinvar	2 clinvar		59
nonsense	2 clinvar	2 clinvar				4
start loss						0
frameshift	4 clinvar		1 clinvar			5
splice donor/acceptor (+/-2bp)			2 clinvar			2
Total	7	2	60	2	0	71

Highest pathogenic variant AF is 0.00001162961

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 17 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_017736.5	RefSeq	NP_060206.2	4	MANE Select
ENST00000396083.7	Ensembl	ENSP00000379392.2	4	MANE Select
NM_001304550.2	RefSeq	NP_001291479.1	4	Standard
ENST00000381337.6	Ensembl	ENSP00000370741.2	4	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

rRNA modification
tRNA modification

Molecular Function

RNA binding
protein binding

Cellular Component

nucleoplasm

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000381337
Coding exons: 4
Length: 8421
Individuals with no LoFs: 125706
Homozygous LoFs: 0
Heterozygous LoFs: 42
Defined: 125748
p: 0.000167

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.476	169	187	0.902	0.00000866	2304
Missense (PolyPhen)		37	48.307	0.76593		639
Synonymous	0.587	66	72.4	0.912	0.00000359	659
Loss of Function	-0.211	17	16.1	1.06	8.95e-7	198

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000062	0.000062	rare
Latino/Admixed American	0.00014	0.00014	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00022	0.00022	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.00019	0.00019	rare
South Asian	0.00033	0.00033	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Functions as a tRNA-binding adapter to mediate NAT10- dependent tRNA acetylation (PubMed:25653167). {ECO:0000269|PubMed:25653167}.;

Recessive Scores

pRec: 0.119

Intolerance Scores

LoFtool: 0.555
RVIS EVS: -0.11
RVIS percentile EVS: 45.26

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.662

Gene Damage Prediction

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