STYXL2

Chr 1

serine/threonine/tyrosine interacting like 2

Also known as: DUSP27

NCBI Gene: 92235 ENSG00000198842 UniProt: Q5VZP5 OMIM: 621374

This protein is predicted to function as a MAP kinase phosphatase that negatively regulates MAPK signaling and may be required for myofiber maturation in skeletal muscle. The gene shows extremely low constraint against loss-of-function variants (pLI near 0), suggesting that complete loss of function is well-tolerated in humans. No clearly established Mendelian diseases have been definitively linked to STYXL2 mutations in the current literature.

OMIM ResearchSummary from RefSeq, UniProt

Predicted to enable MAP kinase phosphatase activity and protein tyrosine/serine/threonine phosphatase activity. Predicted to be involved in negative regulation of MAPK cascade. Predicted to be located in sarcomere. Predicted to be active in cytoplasm. [provided by Alliance of Genome Resources, Jul 2025]

OMIM ResearchGenerating clinical summary…

MultiplemechanismLOEUF 1.11

Clinical Summary— STYXL2

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

233 VUS of 267 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.11LOEUF

pLI 0.000

Z-score 0.98

OE 0.83 (0.63–1.11)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.60Z-score

OE missense 1.07 (1.00–1.13)

708 obs / 664.2 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.83 (0.63–1.11)

0≤0.351.4

Missense OE?1.07 (1.00–1.13)

0≤0.61.4

Synonymous OE?1.02

0≤1.21.6

LoF obs/exp: 32 / 38.5Missense obs/exp: 708 / 664.2Syn Z: -0.30

This gene — mechanism propensity

0.80top 10%

GOF

0.6736th %ile

LOF

0.3164th %ile

This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to dominant-negative as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

DNprediction above median

GOFprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

267 submitted variants in ClinVar

ClinVar

Classification Summary

VUS233

Likely Benign16

Benign6

Conflicting2

233

VUS

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	0	0	0	0
Likely Pathogenic	0	0	0	0	0
VUS	1	232	0	0	233
Likely Benign	0	14	0	2	16
Benign	0	1	1	4	6
Conflicting	—				2
Total	1	247	1	6	257

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

18 pathogenic / likely-pathogenic (of 20) ClinVar copy-number / structural variants overlap STYXL2 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →