DYNC1LI1

Chr 3

dynein cytoplasmic 1 light intermediate chain 1

Also known as: DLC-A, DLIC-1, DNCLI1, LIC1

NCBI Gene: 51143 ENSG00000144635 UniProt: Q9Y6G9

The encoded protein is a light intermediate chain subunit of the cytoplasmic dynein 1 complex that facilitates retrograde transport of vesicles and organelles along microtubules and is required for spindle assembly checkpoint progression during mitosis. Mutations cause autosomal dominant intellectual disability with neurologic and ophthalmologic features. This gene is highly constrained against loss-of-function variants, indicating that such mutations are likely to be pathogenic.

ResearchSummary from RefSeq, UniProt

The protein encoded by this gene belongs to light intermediate subunit family, whose members are components of the multiprotein cytoplasmic dynein complex, which is involved in intracellular trafficking and chromosome segregation during mitosis. The protein plays a role in moving the spindle assembly checkpoint (SAC) from kinetochores to spindle poles. The protein may also mediate binding to other cargo molecules to facilitate intracellular vesicle trafficking. [provided by RefSeq, Jul 2016]

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

0.33

LOEUF· LoF intol.

LOF

Mechanism· predicted

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

0.33LOEUF

pLI 0.963

Z-score 4.20

OE 0.14 (0.07–0.33)

Highly constrained

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

Missense Constraint?

1.04Z-score

OE missense 0.82 (0.73–0.92)

221 obs / 269.0 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.14 (0.07–0.33)

0≤0.351.4

Missense OE?0.82 (0.73–0.92)

0≤0.61.4

Synonymous OE?0.92

0≤1.21.6

LoF obs/exp: 4 / 27.9Missense obs/exp: 221 / 269.0Syn Z: 0.66

Background carrier burden — how many people carry a rare variant somewhere in DYNC1LI1?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 92

666 rare PASS variants

Rare truncating (LoF)

1 in 1,600

54 rare PASS variants

Rare synonymous (reference)

1 in 130

275 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for DYNC1LI1. 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 130	1 in 2,100
South Asian	~43k	1 in 87	1 in 930
Remaining (unassigned)	~30k	1 in 80	1 in 3,300
European (Finnish)	~27k	1 in 240	1 in 2,000
Admixed American	~22k	1 in 56	1 in 880
African / African American	~21k	1 in 74	1 in 2,000
East Asian	~20k	1 in 85	1 in 580
Ashkenazi Jewish	~13k	1 in 270	≈ 1 in 3,200
Middle Eastern	~2,884	1 in 95	≈ 1 in 800

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): 10 of 13 coding exons well covered in gnomAD exomes; exons 3, 6, 7 marginal. Genomes: all 13.? see exons ↓