STYX

protein-coding

serine/threonine/tyrosine interacting protein, the group of Atypical dual specificity phosphatases

Gene summary

The protein encoded by this gene is a pseudophosphatase, able to bind potential substrates but lacking an active catalytic loop. The encoded protein may be involved in spermiogenesis. Two transcript variants encoding the same protein have been found for these genes. [provided by RefSeq, Oct 2011]

MANE transcript

NM_145251.4

Inheritance

—

ClinVar variants

U:31

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.22

Max pathogenic AF

—

Genomic locus

chr14:52,730,166-52,774,989

External References & Databases

Ensembl (ENSG00000198252)

Transcript & Mutation Effects

hg38 • Region Span ~44.8 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 STYX variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 25

not providedTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_145251.4. 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						0
missense			27 clinvar			27
nonsense			1 clinvar			1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			3 clinvar			3
Total	0	0	31	0	0	31

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 29 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_145251.4	RefSeq	NP_660294.1	11	MANE Select
ENST00000354586.5	Ensembl	ENSP00000346599.4	11	MANE Select
NM_001130701.2	RefSeq	NP_001124173.1	11	Standard
ENST00000442123.6	Ensembl	ENSP00000403214.2	11	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

protein dephosphorylation
negative regulation of protein binding
negative regulation of catalytic activity
MAPK export from nucleus
negative regulation of SCF-dependent proteasomal ubiquitin-dependent catabolic process

Molecular Function

pseudophosphatase activity
protein binding
protein tyrosine/serine/threonine phosphatase activity
F-box domain binding

Cellular Component

nucleus
nucleoplasm
cytoplasm
cytosol

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000354586
Coding exons: 11
Length: 44819
Individuals with no LoFs: 125706
Homozygous LoFs: 0
Heterozygous LoFs: 6
Defined: 125712
p: 0.0000239

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.47	72	117	0.616	0.00000538	1472
Missense (PolyPhen)		13	31.239	0.41615		422
Synonymous	0.113	35	35.9	0.976	0.00000163	376
Loss of Function	3.04	4	17.9	0.224	8.58e-7	216

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0.000099	0.000099	rare
East Asian	0.000067	0.000054	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.000029	0.000026	rare
South Asian	0.000033	0.000033	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Catalytically inactive phosphatase (PubMed:23847209). Acts as a nuclear anchor for MAPK1/MAPK3 (ERK1/ERK2) (PubMed:23847209). Modulates cell-fate decisions and cell migration by spatiotemporal regulation of MAPK1/MAPK3 (ERK1/ERK2) (PubMed:23847209). By binding to the F-box of FBXW7, prevents the assembly of FBXW7 into the SCF E3 ubiquitin-protein ligase complex, and thereby inhibits degradation of its substrates (PubMed:28007894). Plays a role in spermatogenesis (By similarity). {ECO:0000250|UniProtKB:Q60969, ECO:0000269|PubMed:23847209, ECO:0000269|PubMed:28007894}.;

Recessive Scores

pRec: 0.105

Intolerance Scores

LoFtool: 0.307
RVIS EVS: -0.16
RVIS percentile EVS: 41.25

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.307

Gene Damage Prediction

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