SASS6

Chr 1

SAS-6 centriolar assembly protein

Also known as: MCPH14, SAS-6, SAS6

NCBI Gene: 163786 ENSG00000156876 UniProt: Q6UVJ0

The protein forms the central hub and spokes of the cartwheel-shaped centriole structure and is essential for centriole duplication and function within the centrosome. Mutations cause autosomal recessive primary microcephaly 14 through a loss-of-function mechanism that disrupts normal centriole formation and cell division.

ResearchSummary from RefSeq, OMIM, UniProt, Mechanism

The protein encoded by this gene is a central component of centrioles and is necessary for their duplication and function. Centrioles adopt a cartwheel-shaped structure, with the encoded protein forming the hub and spokes inside a microtubule cylinder. Defects in this gene are a cause of autosomal recessive primary microcephaly. [provided by RefSeq, Oct 2016]

ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtMicrocephaly 14, primary, autosomal recessive

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.68

LOEUF

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

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.68LOEUF

pLI 0.000

Z-score 3.15

OE 0.46 (0.32–0.68)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

1.01Z-score

OE missense 0.84 (0.76–0.93)

261 obs / 311.0 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.46 (0.32–0.68)

0≤0.351.4

Missense OE?0.84 (0.76–0.93)

0≤0.61.4

Synonymous OE?1.03

0≤1.21.6

LoF obs/exp: 18 / 39.3Missense obs/exp: 261 / 311.0Syn Z: -0.24

Background carrier burden — how many people carry a rare variant somewhere in SASS6?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 110

751 rare PASS variants

Rare truncating (LoF)

1 in 570

147 rare PASS variants

Rare synonymous (reference)

1 in 220

283 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for SASS6. 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 170	1 in 650
South Asian	~43k	1 in 87	1 in 840
Remaining (unassigned)	~30k	1 in 100	1 in 540
European (Finnish)	~27k	1 in 440	1 in 2,200
Admixed American	~22k	1 in 76	1 in 510
African / African American	~21k	1 in 86	1 in 610
East Asian	~20k	1 in 140	1 in 680
Ashkenazi Jewish	~13k	1 in 1,200	1 in 620
Middle Eastern	~2,884	1 in 82	≈ 1 in 1,400

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): 5 of 17 coding exons well covered in gnomAD exomes; exon 12 poorly covered; exons 2, 3, 4, 5, 6 and 6 more marginal. Genomes: all 17.? see exons ↓