TPST2

protein-coding

tyrosylprotein sulfotransferase 2, the group of Sulfotransferases, membrane bound|MicroRNA protein coding host genes

Gene summary

The protein encoded by this gene catalyzes the O-sulfation of tyrosine residues within acidic regions of proteins. The encoded protein is a type II integral membrane protein found in the Golgi body. Alternative splicing produces multiple transcript variants encoding distinct isoforms. [provided by RefSeq, May 2018]

MANE transcript

NM_003595.5

Inheritance

—

ClinVar variants

U:59

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.25

Max pathogenic AF

—

Genomic locus

chr22:26,521,996-26,596,717

External References & Databases

Ensembl (ENSG00000128294)

Transcript & Mutation Effects

hg38 • Region Span ~74.7 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 TPST2 variants in ClinVar

1 Conditions Cataloged

not specifiedTotal: 52

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_003595.5. 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			2 clinvar			2
missense			54 clinvar			54
nonsense			1 clinvar			1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			2 clinvar			2
Total	0	0	59	0	0	59

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 127 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_003595.5	RefSeq	NP_003586.3	4	MANE Select
ENST00000338754.9	Ensembl	ENSP00000339813.4	4	MANE Select
NM_001008566.3	RefSeq	NP_001008566.1	4	Standard
NM_001362922.2	RefSeq	NP_001349851.1	4	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Phase II - Conjugation of compounds
Biological oxidations
Metabolism
Cytosolic sulfonation of small molecules

Biological Process

peptidyl-tyrosine sulfation
3'-phosphoadenosine 5'-phosphosulfate metabolic process

Molecular Function

protein-tyrosine sulfotransferase activity
protein homodimerization activity

Cellular Component

Golgi membrane
endoplasmic reticulum
Golgi apparatus
integral component of membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000338754
Coding exons: 4
Length: 71224
Individuals with no LoFs: 125742
Homozygous LoFs: 0
Heterozygous LoFs: 5
Defined: 125747
p: 0.0000199

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.21	204	259	0.788	0.0000184	2391
Missense (PolyPhen)		44	77.79	0.56563		743
Synonymous	-0.520	122	115	1.06	0.00000855	794
Loss of Function	2.43	3	12.2	0.247	5.16e-7	143

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0.000038	0.000035	rare
South Asian	0	0.0	absent
Other	0.00018	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Catalyzes the O-sulfation of tyrosine residues within acidic motifs of polypeptides, using 3'-phosphoadenylyl sulfate (PAPS) as cosubstrate. {ECO:0000269|PubMed:9733778}.;

Recessive Scores

pRec: 0.122

Intolerance Scores

LoFtool: 0.113
RVIS EVS: -0.84
RVIS percentile EVS: 11.18

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.300

Gene Damage Prediction

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