THUMPD1

Chr 16AR

THUMP domain 1 NAT10 acetyltransferase adaptor

Also known as: NEDSOA, Tan1

NCBI Gene: 55623 ENSG00000066654 UniProt: Q9NXG2 OMIM: 616662

The protein functions as a tRNA-binding adapter that mediates tRNA acetylation by facilitating the modification of cytidine to N4-acetylcytidine. Mutations cause autosomal recessive neurodevelopmental disorder with speech delay and variable ocular anomalies. This gene is highly intolerant to loss-of-function variants, indicating its critical role in normal development.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

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]

OMIM ResearchGenerating clinical summary…

ARLOEUF 1.581 OMIM phenotype

Clinical Summary— THUMPD1

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

8 unique Pathogenic / Likely Pathogenic· 57 VUS of 73 total submissions

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.58LOEUF

pLI 0.000

Z-score -0.21

OE 1.06 (0.72–1.58)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.48Z-score

OE missense 0.90 (0.80–1.02)

169 obs / 187.4 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?1.06 (0.72–1.58)

0≤0.351.4

Missense OE?0.90 (0.80–1.02)

0≤0.61.4

Synonymous OE?0.91

0≤1.21.6

LoF obs/exp: 17 / 16.1Missense obs/exp: 169 / 187.4Syn Z: 0.59

ClinVar Variant Classifications

73 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic7

Likely Pathogenic1

VUS57

Likely Benign2

Conflicting1

Pathogenic

Likely Pathogenic

VUS

Likely Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	6	1	0	0	7
Likely Pathogenic	0	1	0	0	1
VUS	1	56	0	0	57
Likely Benign	0	2	0	0	2
Benign	0	0	0	0	0
Conflicting	—				1
Total	7	60	0	0	68

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

14 pathogenic / likely-pathogenic (of 21) ClinVar copy-number / structural variants overlap THUMPD1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →