PHPT1

protein-coding

phosphohistidine phosphatase 1, the group of Protein phosphatases

Gene summary

This gene encodes an enzyme that catalyzes the reversible dephosphorylation of histidine residues in proteins. It may be involved in the dephosphorylation of G-beta and ATP citrate lyase and in negatively regulating CD4 T lymphocytes by dephosphorylation and inhibition of KCa3.1 channels. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2013]

MANE transcript

NM_014172.6

Inheritance

—

ClinVar variants

U:32B:5

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 1.1

Max pathogenic AF

—

Genomic locus

chr9:136,848,724-136,851,027

External References & Databases

Ensembl (ENSG00000054148)

Transcript & Mutation Effects

hg38 • Region Span ~2.3 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 PHPT1 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 32

not providedTotal: 3

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_014172.6. 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				2 clinvar		2
missense			32 clinvar	2 clinvar	1 clinvar	35
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	32	4	1	37

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 28 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_014172.6	RefSeq	NP_054891.2	3	MANE Select
ENST00000247665.12	Ensembl	ENSP00000247665.10	3	MANE Select
NM_001135861.3	RefSeq	NP_001129333.1	4	Standard
NM_001287342.2	RefSeq	NP_001274271.1	3	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Fructose intolerance, hereditary
Fructose and Mannose Degradation
Fructosuria
EGFR1

Biological Process

protein dephosphorylation
positive regulation of insulin secretion involved in cellular response to glucose stimulus
peptidyl-histidine dephosphorylation
negative regulation of T cell receptor signaling pathway
negative regulation of lyase activity

Molecular Function

protein binding
calcium channel inhibitor activity
ion channel binding
protein histidine phosphatase activity

Cellular Component

cytosol
extracellular exosome

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000247665
Coding exons: 3
Length: 2313
Individuals with no LoFs: 125469
Homozygous LoFs: 0
Heterozygous LoFs: 71
Defined: 125540
p: 0.000283

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.352	91	82.0	1.11	0.00000451	812
Missense (PolyPhen)		36	35.884	1.0032		336
Synonymous	-2.49	56	36.8	1.52	0.00000259	235
Loss of Function	-0.216	6	5.46	1.10	2.36e-7	59

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00012	0.00012	rare
Latino/Admixed American	0.00023	0.00023	rare
Ashkenazi Jewish	0.0010	0.00099	rare
East Asian	0.00022	0.00022	rare
Finnish	0.00051	0.00051	rare
European (Non-Finnish)	0.00022	0.00022	rare
South Asian	0.00033	0.00033	rare
Other	0.00016	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Exhibits phosphohistidine phosphatase activity. {ECO:0000269|PubMed:19836471, ECO:0000269|PubMed:25574816}.;

Intolerance Scores

LoFtool: 0.341
RVIS EVS: 0.13
RVIS percentile EVS: 63.2

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.813

Gene Damage Prediction

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