SASS6

protein-coding

SAS-6 centriolar assembly protein

Gene summary

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]

MANE transcript

NM_194292.3

Inheritance

ClinVar variants

P:8U:82B:25

Top phenotype

Microcephaly 14, primary, autosomal recessive

gnomAD constraint

pLI —, LoF o/e 0.46

Max pathogenic AF

—

Genomic locus

chr1:100,083,563-100,132,955

External References & Databases

Ensembl (ENSG00000156876)

Transcript & Mutation Effects

hg38 • Region Span ~49.4 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

microcephaly 14, primary, autosomal recessiveMODERATE

Inheritance Pattern: AR

Disease ID:MONDO:0014623

Submitter: G2P

microcephaly 14, primary, autosomal recessiveMODERATE

Inheritance Pattern: AR

Disease ID:MONDO:0014623

Submitter: Ambry Genetics

microcephaly 14, primary, autosomal recessiveSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0014623

Submitter: Labcorp Genetics (formerly Invitae)

microcephaly 14, primary, autosomal recessiveSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0014623

Submitter: PanelApp Australia

autosomal recessive primary microcephalySUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0016660

Submitter: Orphanet

Clinical Genomic Database (CGD)

Microcephaly 14, primary, autosomal recessiveAR

Manifestation: Neurologic

Intervention: General

Rationale: Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing

Refs: 24951542; 30639237

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to SASS6 variants in ClinVar

5 Conditions Cataloged

Inborn genetic diseasesTotal: 84

not providedTotal: 32

Microcephaly 14, primary, autosomal recessiveTotal: 13

SASS6-related disorderTotal: 11

not specifiedTotal: 9

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_194292.3. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous				10 clinvar	3 clinvar	13
missense	1 clinvar		77 clinvar	12 clinvar		90
nonsense		1 clinvar				1
start loss						0
frameshift	1 clinvar	3 clinvar	2 clinvar			6
splice donor/acceptor (+/-2bp)	1 clinvar	1 clinvar	3 clinvar			5
Total	3	5	82	22	3	115

Highest pathogenic variant AF is 0.00017193948

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 11 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_194292.3	RefSeq	NP_919268.1	17	MANE Select
ENST00000287482.6	Ensembl	ENSP00000287482.5	17	MANE Select
NM_001304829.2	RefSeq	NP_001291758.1	12	Standard
ENST00001069572.1	Ensembl	ENSP00000739378.1	17	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
sass6	Danio rerio	Structure: sperm Quality: composition abnormal

Gene / Model

Organism

Observed Phenotype

sass6

Danio rerio

Structure: sperm

Quality: composition

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

centriole replication
centrosome duplication

Molecular Function

protein binding

Cellular Component

centrosome
centriole
microtubule organizing center
cytosol
deuterosome

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000287482
Coding exons: 17
Length: 49393
Individuals with no LoFs: 125647
Homozygous LoFs: 1
Heterozygous LoFs: 99
Defined: 125747
p: 0.000398

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.01	261	311	0.839	0.0000150	4277
Missense (PolyPhen)		38	65.64	0.57892		965
Synonymous	-0.239	123	120	1.03	0.00000607	1185
Loss of Function	3.15	18	39.3	0.458	0.00000192	507

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00019	0.00018	rare
Latino/Admixed American	0.00021	0.00020	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00023	0.00022	rare
Finnish	0.000046	0.000046	rare
European (Non-Finnish)	0.00042	0.00040	rare
South Asian	0.0012	0.0011	notable
Other	0.00085	0.00081	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Central scaffolding component of the centrioles ensuring their 9-fold symmetry. Required for centrosome biogenesis and duplication: required both for mother-centriole-dependent centriole duplication and deuterosome-dependent centriole amplification in multiciliated cells. Overexpression results in excess foci-bearing centriolar markers. Required for the recruitment of STIL to the procentriole and for STIL-mediated centriole amplification (PubMed:22020124). {ECO:0000269|PubMed:15665853, ECO:0000269|PubMed:16244668, ECO:0000269|PubMed:17681131, ECO:0000269|PubMed:22020124}.;
Disease: DISEASE: Microcephaly 14, primary, autosomal recessive (MCPH14) [MIM:616402]: A form of microcephaly, a disease defined as a head circumference more than 3 standard deviations below the age, sex and ethnically matched mean. Brain weight is markedly reduced and the cerebral cortex is disproportionately small. {ECO:0000269|PubMed:24951542}. Note=The disease is caused by mutations affecting the gene represented in this entry.;

Recessive Scores

pRec: 0.0930

Intolerance Scores

LoFtool: 0.675
RVIS EVS: -0.25
RVIS percentile EVS: 36.07

Essentials

Essential (CRISPR): N
Essential (CRISPR2): S
Essential (gene trap): E
Indispensability pred.: E
Indispensability score: 0.955

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	High
Cancer	Medium	Medium	Medium