THUMPD1

THUMP domain containing 1

Basic information

Region (hg38): 16:20702815-20742084

Links

ENSG00000066654 ∙ NCBI:55623 ∙ OMIM:616662 ∙ HGNC:23807 ∙ Uniprot:Q9NXG2 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• neurodevelopmental disorder with speech delay and variable ocular anomalies (Moderate), mode of inheritance: AR
• neurodevelopmental disorder with speech delay and variable ocular anomalies (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Neurodevelopmental disorder with speech delay and variable ocular anomalies	AR	General	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	Craniofacial; Dental; Musculoskeletal; Neurologic; Ophthalmologic	30237576; 35196516

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the THUMPD1 gene.

• Neurodevelopmental disorder (6 variants)
• Neurodevelopmental disorder with speech delay and variable ocular anomalies (4 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the THUMPD1 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous						0
missense	1		20	1		22
nonsense	2					2
start loss						0
frameshift	4					4
inframe indel		1				1
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	7	1	20	1	0

Highest pathogenic variant AF is 0.0000131

Variants in THUMPD1

This is a list of pathogenic ClinVar variants found in the THUMPD1 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
16-20736891-C-A		Inborn genetic diseases	Uncertain significance (Apr 18, 2024)
16-20736908-G-C		Inborn genetic diseases	Uncertain significance (Aug 11, 2022)
16-20736978-T-C		Inborn genetic diseases	Uncertain significance (Feb 22, 2023)
16-20737067-G-C		Inborn genetic diseases	Likely benign (Jan 29, 2024)
16-20737094-T-A		Neurodevelopmental disorder with speech delay and variable ocular anomalies	Uncertain significance (Apr 04, 2024)
16-20737098-C-T		Inborn genetic diseases	Uncertain significance (Apr 12, 2024)
16-20737165-AAAC-A		Neurodevelopmental disorder • Neurodevelopmental disorder with speech delay and variable ocular anomalies	Likely pathogenic (Dec 15, 2021)
16-20737199-C-A		Inborn genetic diseases	Uncertain significance (Dec 19, 2022)
16-20737206-C-A		Inborn genetic diseases	Uncertain significance (Jan 26, 2023)
16-20737236-G-A		Neurodevelopmental disorder • Neurodevelopmental disorder with speech delay and variable ocular anomalies • Inborn genetic diseases	Conflicting classifications of pathogenicity (Dec 01, 2023)
16-20737244-G-T		Inborn genetic diseases	Uncertain significance (Jul 20, 2021)
16-20737728-T-TC		Neurodevelopmental disorder • Neurodevelopmental disorder with speech delay and variable ocular anomalies	Pathogenic (Dec 21, 2023)
16-20737746-C-T		Inborn genetic diseases	Uncertain significance (Mar 08, 2024)
16-20737761-T-G		Inborn genetic diseases	Uncertain significance (Mar 20, 2024)
16-20737852-C-G		Inborn genetic diseases	Uncertain significance (Jun 10, 2022)
16-20737867-A-AG		Neurodevelopmental disorder • Neurodevelopmental disorder with speech delay and variable ocular anomalies	Pathogenic (Dec 15, 2021)
16-20737873-G-A		Neurodevelopmental disorder	Pathogenic (Dec 15, 2021)
16-20737878-A-G		Inborn genetic diseases	Uncertain significance (May 08, 2023)
16-20737894-G-A		Neurodevelopmental disorder	Pathogenic (Dec 15, 2021)
16-20737920-A-G		Inborn genetic diseases	Uncertain significance (Jan 30, 2024)
16-20738924-C-T		Inborn genetic diseases	Uncertain significance (Apr 23, 2024)
16-20738962-A-C		Neurodevelopmental disorder	Pathogenic (Dec 15, 2021)
16-20738996-CTTCT-C		Neurodevelopmental disorder • Neurodevelopmental disorder with speech delay and variable ocular anomalies	Pathogenic (Dec 15, 2021)
16-20739012-AG-A		Neurodevelopmental disorder with speech delay and variable ocular anomalies	Pathogenic (Nov 15, 2023)
16-20739050-G-A		Inborn genetic diseases	Uncertain significance (Jun 22, 2021)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
THUMPD1	protein_coding	protein_coding	ENST00000381337	4	8421

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
3.97e-12	0.0259	125706	0	42	125748	0.000167

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.476	169	187	0.902	0.00000866	2304
Missense in 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

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000206	0.000206
Ashkenazi Jewish	0.00	0.00
East Asian	0.000217	0.000217
Finnish	0.00	0.00
European (Non-Finnish)	0.000194	0.000193
Middle Eastern	0.000217	0.000217
South Asian	0.000327	0.000327
Other	0.00	0.00

dbNSFP

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

Haploinsufficiency Scores

• pHI: 0.601
• hipred: N
• hipred_score: 0.292
• ghis: 0.642

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.662

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Thumpd1

Gene ontology

• Biological process: rRNA modification;tRNA modification
• Cellular component: nucleoplasm
• Molecular function: RNA binding;protein binding