THTPA

protein-coding

thiamine triphosphatase

Gene summary

This gene encodes an enzyme which catalyzes the biosynthesis of thiamine disphophate (vitamin B1) by hydrolysis of thiamine triphosphate. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2011]

MANE transcript

NM_024328.6

Inheritance

—

ClinVar variants

U:30B:1

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.9

Max pathogenic AF

—

Genomic locus

chr14:23,555,988-23,560,271

External References & Databases

Ensembl (ENSG00000259431)

Transcript & Mutation Effects

hg38 • Region Span ~4.3 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to THTPA variants in ClinVar

1 Conditions Cataloged

not specifiedTotal: 30

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_024328.6. 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			1 clinvar			1
missense			29 clinvar	1 clinvar		30
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	30	1	0	31

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 20 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_024328.6	RefSeq	NP_077304.1	2	MANE Select
ENST00000288014.7	Ensembl	ENSP00000288014.6	2	MANE Select
NM_001126339.3	RefSeq	NP_001119811.1	2	Standard
NM_001256062.2	RefSeq	NP_001242991.1	2	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Thiamine metabolism - Homo sapiens (human)
Thiamine Metabolism
Vitamin B1 (thiamin) metabolism
Metabolism
Metabolism of water-soluble vitamins and cofactors

Biological Process

generation of precursor metabolites and energy
thiamine metabolic process
dephosphorylation
thiamine diphosphate metabolic process
thiamine-containing compound metabolic process

Molecular Function

magnesium ion binding
hydrolase activity
thiamin-triphosphatase activity

Cellular Component

cytosol

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000288014
Coding exons: 2
Length: 4265
Individuals with no LoFs: 125720
Homozygous LoFs: 0
Heterozygous LoFs: 28
Defined: 125748
p: 0.000111

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.334	143	132	1.08	0.00000721	1455
Missense (PolyPhen)		44	41.34	1.0643		484
Synonymous	0.810	46	53.5	0.859	0.00000267	500
Loss of Function	0.298	9	10.0	0.899	7.49e-7	84

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000062	0.000062	rare
Latino/Admixed American	0.000058	0.000058	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00022	0.00022	rare
Finnish	0.000047	0.000046	rare
European (Non-Finnish)	0.000098	0.000097	rare
South Asian	0.00027	0.00026	rare
Other	0.00016	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Hydrolase highly specific for thiamine triphosphate (ThTP). {ECO:0000269|PubMed:11827967, ECO:0000269|PubMed:23707715}.;

Recessive Scores

pRec: 0.121

Intolerance Scores

LoFtool: 0.892
RVIS EVS: -0.25
RVIS percentile EVS: 35.75

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.895

Gene Damage Prediction

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