SPINDOC

Chr 11

spindlin interactor and repressor of chromatin binding

Also known as: C11orf84, SPIN-DOC

NCBI Gene: 144097 ENSG00000168005 UniProt: Q9BUA3 OMIM: 621257

The SPINDOC protein stabilizes SPIN1 and enhances its binding to methylated histones, while also facilitating PARP1 activity in DNA damage response through regulation of poly-ADP-ribosylation. Mutations cause autosomal dominant neurodevelopmental disorders with intellectual disability, developmental delay, and seizures. This gene is highly constrained against loss-of-function mutations (pLI=0.99, LOEUF=0.21), indicating that even single functional copies are critical for normal development.

OMIM ResearchSummary from RefSeq, UniProt

Involved in DNA damage response and negative regulation of DNA-templated transcription. Is active in nucleus and site of DNA damage. [provided by Alliance of Genome Resources, Jul 2025]

OMIM ResearchGenerating clinical summary…

Clinical highlights

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.21

LOEUF· LoF intol.

LOF

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

0.21LOEUF

pLI 0.991

Z-score 3.50

OE 0.00 (0.00–0.21)

Highly constrained

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

Missense Constraint?

0.67Z-score

OE missense 0.88 (0.78–0.98)

204 obs / 232.8 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.00 (0.00–0.21)

0≤0.351.4

Missense OE?0.88 (0.78–0.98)

0≤0.61.4

Synonymous OE?1.07

0≤1.21.6

LoF obs/exp: 0 / 14.3Missense obs/exp: 204 / 232.8Syn Z: -0.57

Background carrier burden — how many people carry a rare variant somewhere in SPINDOC?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 92

501 rare PASS variants

Rare truncating (LoF)

1 in 3,600

50 rare PASS variants

Rare synonymous (reference)

1 in 140

250 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for SPINDOC. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 140	1 in 3,900
South Asian	~43k	1 in 80	≈ 1 in 13,000
Remaining (unassigned)	~30k	1 in 89	1 in 4,400
European (Finnish)	~27k	1 in 680	≈ 1 in 8,900
Admixed American	~22k	1 in 95	≈ 1 in 4,500
African / African American	~21k	1 in 88	1 in 3,000
East Asian	~20k	1 in 120	1 in 840
Ashkenazi Jewish	~13k	1 in 800	≈ 1 in 13,000
Middle Eastern	~2,884	1 in 81	≈ 1 in 2,900

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): All 6 coding exons well covered in gnomAD exomes and genomes.? see exons ↓