YIPF5

Chr 5AR

Yip1 domain family member 5

Also known as: FinGER5, MEDS2, SB140, SMAP-5, SMAP5, YIP1A, YIPFalpha1A

NCBI Gene: 81555ENSG00000145817UniProt: Q969M3

Involved in insulin processing and regulation of ER to Golgi vesicle-mediated transport. Located in Golgi apparatus; endoplasmic reticulum; and nucleoplasm. [provided by Alliance of Genome Resources, Jul 2025]

Primary Disease Associations & Inheritance

Microcephaly, epilepsy, and diabetes syndrome 2MIM #619278
AR
58
ClinVar variants
17
Pathogenic / LP
0.99
pLI score· haploinsufficient
0
Active trials
Clinical Summary— YIPF5
⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.99). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
17 Pathogenic / Likely Pathogenic· 37 VUS of 58 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.23LOEUF
pLI 0.985
Z-score 3.31
OE 0.00 (0.00–0.23)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
0.68Z-score
OE missense 0.84 (0.72–0.98)
112 obs / 134.1 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.00 (0.00–0.23)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.84 (0.72–0.98)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.78
0≤1.21.6
LoF obs/exp: 0 / 12.8Missense obs/exp: 112 / 134.1Syn Z: 1.25

ClinVar Variant Classifications

58 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic17
VUS37
Likely Benign2
Benign2
17
Pathogenic
37
VUS
2
Likely Benign
2
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
4
13
0
17
Likely Pathogenic
0
0
0
0
0
VUS
0
33
4
0
37
Likely Benign
0
0
1
1
2
Benign
0
2
0
0
2
Total03918158

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

View in ClinVar →

Protein Context — Lollipop Plot

YIPF5 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Microcephaly, epilepsy, and diabetes syndrome 2

MIM #619278

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools