GORAB

Chr 1AR

golgin, RAB6 interacting

Also known as: GO, NTKLBP1, SCYL1BP1

NCBI Gene: 92344 ENSG00000120370 UniProt: Q5T7V8 OMIM: 607983

The protein is a golgin family member that localizes to the Golgi apparatus and functions in the secretory pathway, with additional cytoplasmic localization suggesting a role in mitosis. Mutations cause geroderma osteodysplasticum, a rare connective tissue disorder affecting skin and bone development, inherited in an autosomal recessive pattern. The gene shows minimal constraint against loss-of-function variants (pLI near 0, LOEUF ~1.0), consistent with its recessive inheritance pattern.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM

This gene encodes a member of the golgin family, a group of coiled-coil proteins localized to the Golgi. The encoded protein may function in the secretory pathway. The encoded protein, which also localizes to the cytoplasm, was identified by interactions with the N-terminal kinase-like protein, and thus it may function in mitosis. Mutations in this gene have been associated with geroderma osteodysplastica. Alternatively spliced transcript variants have been described. [provided by RefSeq, Mar 2009]

GeneReviews OMIM ResearchGenerating clinical summary…

LOFmechanismARLOEUF 0.991 OMIM phenotype

Clinical Summary— GORAB

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Gene-Disease Validity (ClinGen)

geroderma osteodysplastica · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

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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

52 unique Pathogenic / Likely Pathogenic· 162 VUS of 429 total submissions

Explore recent and relevant literature in Research Assistant →

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GeneReview available — GORAB

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.99LOEUF

pLI 0.000

Z-score 1.61

OE 0.60 (0.37–0.99)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

-0.18Z-score

OE missense 1.03 (0.93–1.16)

223 obs / 215.6 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.60 (0.37–0.99)

0≤0.351.4

Missense OE?1.03 (0.93–1.16)

0≤0.61.4

Synonymous OE?1.16

0≤1.21.6

LoF obs/exp: 11 / 18.4Missense obs/exp: 223 / 215.6Syn Z: -1.09

Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗

definitiveGORAB-related geroderma osteodysplasticumLOFAR

This gene — mechanism propensity

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

0.80top 25%

GOF

0.74top 25%

LOF

0.2775th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

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

ClinVar Variant Classifications

429 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic39

Likely Pathogenic13

VUS162

Likely Benign171

Benign26

Conflicting10

Pathogenic

Likely Pathogenic

162

VUS

171

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	29	1	9	0	39
Likely Pathogenic	11	1	1	0	13
VUS	4	118	40	0	162
Likely Benign	0	5	56	110	171
Benign	0	1	21	4	26
Conflicting	—				10
Total	44	126	127	114	421

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

View in ClinVar →

25 pathogenic / likely-pathogenic (of 31) ClinVar copy-number / structural variants overlap GORAB — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →