YIPF1

Chr 1

Yip1 domain family member 1

Also known as: DJ167A19.1, FinGER1, YIPFbeta3A, Yip5a

NCBI Gene: 54432 ENSG00000058799 UniProt: Q9Y548 OMIM: 617521

The protein is predicted to bind small GTPases and participate in vesicle-mediated transport between cellular compartments including the Golgi apparatus. Mutations cause an autosomal recessive neurodevelopmental disorder characterized by intellectual disability, developmental delay, and seizures. The gene shows moderate constraint against loss-of-function variants (LOEUF 0.77), suggesting some tolerance to functional disruption.

OMIM ResearchSummary from RefSeq

Predicted to enable small GTPase binding activity. Predicted to be involved in vesicle-mediated transport. Located in several cellular components, including Golgi apparatus subcompartment; nucleoplasm; and transport vesicle. [provided by Alliance of Genome Resources, Jul 2025]

OMIM ResearchGenerating clinical summary…

MultiplemechanismLOEUF 0.77

Clinical Summary— YIPF1

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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

47 VUS of 63 total submissions

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.77LOEUF

pLI 0.003

Z-score 2.26

OE 0.41 (0.23–0.77)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

-0.14Z-score

OE missense 1.03 (0.91–1.17)

173 obs / 167.7 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.41 (0.23–0.77)

0≤0.351.4

Missense OE?1.03 (0.91–1.17)

0≤0.61.4

Synonymous OE?0.76

0≤1.21.6

LoF obs/exp: 7 / 17.1Missense obs/exp: 173 / 167.7Syn Z: 1.45

This gene — mechanism propensity

0.7327th %ile

GOF

0.6735th %ile

LOF

0.2678th %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

63 submitted variants in ClinVar

ClinVar

Classification Summary

VUS47

Likely Benign1

VUS

Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Total
Pathogenic	0	0
Likely Pathogenic	0	0
VUS	47	47
Likely Benign	1	1
Benign	0	0
Total	48	48

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

View in ClinVar →

12 pathogenic / likely-pathogenic (of 17) ClinVar copy-number / structural variants overlap YIPF1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →