SASS6

Summary

SASS6 (SAS-6 centriolar assembly protein, HGNC:25403) is a protein-coding gene on chromosome 1p21.2, encoding Spindle assembly abnormal protein 6 homolog (Q6UVJ0). Central scaffolding component of the centrioles ensuring their 9-fold symmetry. It is a selective cancer dependency (DepMap: 89.9% of cell lines).

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.

Source: NCBI Gene 163786 — RefSeq curated summary.

At a glance

• Gene–disease (curated): microcephaly 14, primary, autosomal recessive (Strong, GenCC) — +1 more curated relationship
• GWAS associations: 1
• Clinical variants (ClinVar): 157 total — 3 pathogenic, 3 likely-pathogenic
• Phenotypes (HPO): 24
• Cancer dependency (DepMap): dependent in 89.9% of screened cell lines
• MANE Select transcript: NM_194292

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:25403
Approved symbol	SASS6
Name	SAS-6 centriolar assembly protein
Location	1p21.2
Locus type	gene with protein product
Status	Approved
Aliases	DKFZp761A078, SAS-6, FLJ22097, SAS6
Ensembl gene	ENSG00000156876
Ensembl biotype	protein_coding
OMIM	609321
Entrez	163786

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 1 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000287482, ENST00000462159

RefSeq mRNA: 2 — MANE Select: NM_194292 NM_001304829, NM_194292

CCDS: CCDS764

Canonical transcript exons

ENST00000287482 — 17 exons

Exon	Start	End
ENSE00001028843	100107628	100107717
ENSE00001028845	100107810	100108004
ENSE00003488156	100122380	100122484
ENSE00003502026	100107374	100107553
ENSE00003507732	100085536	100085630
ENSE00003560103	100132750	100132930
ENSE00003570188	100102955	100103083
ENSE00003573315	100123210	100123289
ENSE00003582609	100088139	100088236
ENSE00003603618	100106912	100106993
ENSE00003609600	100120394	100120459
ENSE00003613859	100083570	100085434
ENSE00003616928	100105767	100105903
ENSE00003630610	100110292	100110483
ENSE00003687704	100125882	100125942
ENSE00003689059	100119018	100119137
ENSE00003689099	100121378	100121549

Expression profiles

Bgee: expression breadth ubiquitous, 178 present calls, max score 96.87.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 8.6431 / max 156.1556, expressed in 1473 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
13506	7.9605	1423
13508	0.3564	186
13507	0.3262	175

Top tissues by expression

238 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
oocyte	CL:0000023	96.87	silver quality
secondary oocyte	CL:0000655	93.70	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	84.06	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	82.30	gold quality
ventricular zone	UBERON:0003053	78.09	gold quality
ganglionic eminence	UBERON:0004023	74.12	gold quality
calcaneal tendon	UBERON:0003701	73.80	gold quality
endothelial cell	CL:0000115	73.02	silver quality
rectum	UBERON:0001052	72.71	gold quality
testis	UBERON:0000473	72.12	gold quality
vermiform appendix	UBERON:0001154	71.70	gold quality
right testis	UBERON:0004534	71.60	gold quality
bone marrow cell	CL:0002092	71.37	silver quality
smooth muscle tissue	UBERON:0001135	71.11	gold quality
cortical plate	UBERON:0005343	71.06	gold quality
left testis	UBERON:0004533	71.05	gold quality
cerebellar hemisphere	UBERON:0002245	70.75	gold quality
cerebellar cortex	UBERON:0002129	70.64	gold quality
lymph node	UBERON:0000029	70.43	gold quality
oviduct epithelium	UBERON:0004804	70.38	gold quality
islet of Langerhans	UBERON:0000006	70.19	gold quality
mucosa of transverse colon	UBERON:0004991	70.05	gold quality
bone marrow	UBERON:0002371	69.99	gold quality
stromal cell of endometrium	CL:0002255	69.96	gold quality
leukocyte	CL:0000738	69.82	gold quality
right hemisphere of cerebellum	UBERON:0014890	69.77	gold quality
monocyte	CL:0000576	69.64	gold quality
amniotic fluid	UBERON:0000173	69.61	silver quality
epithelium of nasopharynx	UBERON:0001951	69.60	silver quality
cerebellum	UBERON:0002037	69.08	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	6.53
E-MTAB-6524	no	64.44

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

148 targeting SASS6, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-6870-5P	99.99	68.55	2115
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-433-3P	99.98	69.37	1203
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-4723-5P	99.97	68.70	2034
HSA-MIR-5698	99.97	68.49	2029
HSA-MIR-7111-5P	99.97	68.48	2062
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-559	99.95	72.28	3609
HSA-MIR-548AB	99.95	71.31	3488
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-548AP-5P	99.94	71.14	3489
HSA-MIR-548J-5P	99.94	71.14	3489
HSA-MIR-548A-5P	99.94	71.27	3482

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 89.9% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 24)

• SAS-6 is required for daughter centriole formation in C. elegans. SAS-6 is a coiled-coil protein that is recruited to centrioles at the onset of the centrosome duplication cycle. (PMID:15665853)
• Regulated HsSAS-6 levels normally ensure that each centriole seeds the formation of a single procentriole per cell cycle, thus playing a fundamental role in driving the centrosome duplication cycle and ensuring genome integrity. (PMID:17681132)
• Data show that depletion of hSAS-6 specifically inhibits the formation of CPAP-induced PLSs derived from procentrioles. (PMID:19503075)
• The activity of SCF-FBXW5 is negatively regulated by Polo-like kinase 4 (PLK4), which phosphorylates FBXW5 at Ser 151 to suppress its ability to ubiquitylate HsSAS-6. (PMID:21725316)
• hSAS6 depletion hindered STIL targeting to the procentriole, implying that STIL and hSAS6 are mutually dependent for their centriolar localization. (PMID:22020124)
• STIL cooperates with SAS-6 and PLK4 in the control of centriole number and represents a key centriole duplication factor in human cells. (PMID:22349698)
• Authors propose that CEP135 directly connects the central hub protein, hSAS-6, to the outer microtubules, and suggest that this interaction stabilizes the proper cartwheel structure for further CPAP-mediated centriole elongation. (PMID:23511974)
• HsSAS-6 homodimers are targeted to centrosomes where the local environment and high concentration of HsSAS-6 promote oligomerization, thus initiating procentriole formation. (PMID:24590172)
• A homozygous c.185T>C missense mutation in the HsSAS-6 gene is associated with the cause of autosomal recessive primary microcephaly. (PMID:24951542)
• Our present findings revealed that the upregulation of SASS6 expression is involved in the pathogenesis of CRC and is associated with a poor prognosis among patients with colon cancer. (PMID:26035073)
• SAS6 possesses an intrinsic microtubule assembly promoting activity and its outer exposed C-terminal tail may play critical roles in microtubule assembly and stabilizing microtubule attachment with the centriolar cartwheel. (PMID:26422590)
• expression of wild-type centriolar assembly protein SAS-6 in a SAS-6-depleted background resulted in centriole sizes that are similar to wild type. (PMID:26999736)
• Studies indicate that depletion of any one of the protein kinase polo-like kinase 4 (PLK4) and the two proteins STIL and SAS-6 blocks centriole duplication, and, conversely, overexpression causes centriole amplification. (PMID:27911707)
• the role of SASS6 in the pathogenesis of microcephaly (PMID:30639237)
• Expression regulation of PLK-4 and SAS-6 has a central role in centriole biogenesis. (Review) (PMID:30787112)
• CCDC84 Acetylation Oscillation Regulates Centrosome Duplication by Modulating HsSAS-6 Degradation. (PMID:31722219)
• The ubiquitin ligase FBXW7 targets the centriolar assembly protein HsSAS-6 for degradation and thereby regulates centriole duplication. (PMID:32086376)
• SAS-6 Association with gamma-Tubulin Ring Complex Is Required for Centriole Duplication in Human Cells. (PMID:32442461)
• SASS6 promotes proliferation of esophageal squamous carcinoma cells by inhibiting the p53 signaling pathway. (PMID:32671379)
• Knockdown of SASS6 reduces growth of MDAMB231 triplenegative breast cancer cells through arrest of the cell cycle at the G2/M phase. (PMID:33907854)
• E2F4’s cytoplasmic role in multiciliogenesis is mediated via an N-terminal domain that binds two components of the centriole replication machinery, Deup1 and SAS6. (PMID:34260288)
• Case Report: Prenatal Recurrent Microcephaly and Corpus Callosum Abnormalities in a Chinese Family with Novel Biallelic SASS6 Mutations. (PMID:36739862)
• Novel biallelic SASS6 variants associated with primary microcephaly and fetal growth restriction. (PMID:38501757)
• SASS6 promotes tumor proliferation and is associated with TP53 and immune infiltration in lung adenocarcinoma. (PMID:39443355)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	sass6	ENSDARG00000058346
mus_musculus	Sass6	ENSMUSG00000027959
rattus_norvegicus	Sass6	ENSRNOG00000015211

Protein

Protein identifiers

Spindle assembly abnormal protein 6 homolog — Q6UVJ0 (reviewed: Q6UVJ0)

Alternative names: Spindle assembly defective protein 6

All UniProt accessions (1): Q6UVJ0

UniProt curated annotations — full annotation on UniProt →

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. Not required for centriole formation in embryonic stem cells but necessary to maintain centriole architecture. Required for the recruitment of STIL to the procentriole and for STIL-mediated centriole amplification. Overexpression results in excess foci-bearing centriolar markers.

Subunit / interactions. Nine homodimers form a cartwheel structure with an internal diameter of 23 nm and radial spokes connecting to the microtubule triplets. Forms a complex with CPAP and STIL. Interacts with FBXW5. Interacts with NUP62 and TUBG1 at the centrosome. Interacts with CENATAC; the interaction increases with CENATAC acetylation. Interacts with FZR1; the interaction is regulated by CENATAC and leads to SASS6 proteasomal degradation.

Subcellular location. Cytoplasm. Cytoskeleton. Microtubule organizing center. Centrosome. Centriole.

Post-translational modifications. Ubiquitinated by the SCF(FBXW5) E3 ubiquitin-protein ligase complex during S phase, leading to its degradation and preventing centriole reduplication. Ubiquitinated by the anaphase promoting complex/cyclosome (APC/C) E3 ubiquitin-protein ligase complex, leading to its degradation and preventing centriole reduplication.

Disease relevance. 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. The disease is caused by variants affecting the gene represented in this entry.

Domain organisation. The 35 nM long coiled-coil domain mediates homodimerization while the globular N-terminus links the dimers at an angle of 40 degrees to form the inner ring.

RefSeq proteins (2): NP_001291758, NP_919268* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR032396	SAS-6_N	Domain
IPR038558	SAS-6_N_sf	Homologous_superfamily
IPR041513	SAS6_CC	Domain

Pfam: PF16531, PF18594

UniProt features (28 total): strand 9, helix 4, modified residue 3, sequence variant 2, turn 2, region of interest 2, compositionally biased region 2, chain 1, domain 1, mutagenesis site 1, coiled-coil region 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
6Z4A	X-RAY DIFFRACTION	1.46
6YS4	X-RAY DIFFRACTION	2.11

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6UVJ0-F1	74.36	0.46

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (3): 510, 615, 657

Mutagenesis-validated functional residues (1):

Position	Phenotype
131	fails to multimerize via n-terminus.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 271 (showing top): E2F_Q4, E2F_Q4_01, GOBP_REGULATION_OF_MICROTUBULE_BASED_PROCESS, RODRIGUES_THYROID_CARCINOMA_POORLY_DIFFERENTIATED_UP, E2F4DP1_01, CMYB_01, GOBP_CELL_CYCLE_PHASE_TRANSITION, GOBP_POSITIVE_REGULATION_OF_MITOTIC_CELL_CYCLE, GOBP_MALE_GAMETE_GENERATION, GOBP_POSITIVE_REGULATION_OF_ORGANELLE_ORGANIZATION, GOBP_REGULATION_OF_CELLULAR_COMPONENT_BIOGENESIS, GOCC_MICROTUBULE_ORGANIZING_CENTER, GOBP_POSITIVE_REGULATION_OF_G1_S_TRANSITION_OF_MITOTIC_CELL_CYCLE, GOBP_REGULATION_OF_CENTRIOLE_REPLICATION, GOBP_CENTRIOLE_ASSEMBLY

GO Biological Process (7): centriole replication (GO:0007099), spermatogenesis (GO:0007283), positive regulation of centriole replication (GO:0046601), centrosome duplication (GO:0051298), regulation of mitotic spindle organization (GO:0060236), positive regulation of G1/S transition of mitotic cell cycle (GO:1900087), positive regulation of spindle assembly (GO:1905832)

GO Molecular Function (1): protein binding (GO:0005515)

GO Cellular Component (6): cytoplasm (GO:0005737), centrosome (GO:0005813), centriole (GO:0005814), deuterosome (GO:0098536), procentriole replication complex (GO:0120099), cytoskeleton (GO:0005856)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
intracellular membraneless organelle	3
cell cycle process	2
positive regulation of cytoskeleton organization	2
positive regulation of cell cycle process	2
positive regulation of organelle assembly	2
microtubule organizing center	2
centrosome duplication	1
centriole assembly	1
developmental process involved in reproduction	1
male gamete generation	1
centriole replication	1
regulation of centriole replication	1
centrosome cycle	1
mitotic spindle organization	1
regulation of spindle organization	1
G1/S transition of mitotic cell cycle	1
positive regulation of mitotic cell cycle phase transition	1
positive regulation of cell cycle G1/S phase transition	1
regulation of G1/S transition of mitotic cell cycle	1
spindle assembly	1
regulation of spindle assembly	1
binding	1
intracellular anatomical structure	1
cellular anatomical structure	1
centriole	1
cytoplasm	1
protein-containing complex	1

Protein interactions and networks

STRING

1996 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SASS6	CEP135	Q66GS9	999
SASS6	PLK4	O00444	989
SASS6	CPAP	Q9HC77	989
SASS6	STIL	Q15468	967
SASS6	CCP110	O43303	954
SASS6	CEP152	O94986	930
SASS6	CNTLN	Q9NXG0	821
SASS6	TUBG1	P23258	820
SASS6	PCNT	O95613	791
SASS6	CEP192	Q8TEP8	791
SASS6	CEP295	Q9C0D2	791
SASS6	CETN2	P41208	774
SASS6	CEP63	Q96MT8	762
SASS6	CNTROB	Q8N137	727
SASS6	POC5	Q8NA72	724

IntAct

104 interactions, top by confidence:

A	B	Type	Score
CPAP	STIL	psi-mi:“MI:0914”(association)	0.820
CPAP	CEP135	psi-mi:“MI:0914”(association)	0.700
SASS6	STIL	psi-mi:“MI:0914”(association)	0.650
STIL	SASS6	psi-mi:“MI:0915”(physical association)	0.650
STIL	SASS6	psi-mi:“MI:0914”(association)	0.650
SASS6	CEP135	psi-mi:“MI:0915”(physical association)	0.650
CEP135	SASS6	psi-mi:“MI:0915”(physical association)	0.650
CEP135	SASS6	psi-mi:“MI:0407”(direct interaction)	0.650
SASS6	CEP135	psi-mi:“MI:0914”(association)	0.650
SASS6	ZC3HC1	psi-mi:“MI:0915”(physical association)	0.590
FCHSD2	SASS6	psi-mi:“MI:0915”(physical association)	0.560
SASS6	APBB2	psi-mi:“MI:0915”(physical association)	0.560
SASS6		psi-mi:“MI:0915”(physical association)	0.560
SASS6	PMP22	psi-mi:“MI:0915”(physical association)	0.560
PEX26	SASS6	psi-mi:“MI:0915”(physical association)	0.560
HTT	SASS6	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (236): STIL (Affinity Capture-Western), SASS6 (Affinity Capture-Western), SASS6 (Affinity Capture-MS), SASS6 (Affinity Capture-MS), SASS6 (Affinity Capture-MS), SASS6 (Proximity Label-MS), SASS6 (Proximity Label-MS), ABRACL (Proximity Label-MS), ALMS1 (Proximity Label-MS), APC (Proximity Label-MS), CEP131 (Proximity Label-MS), CCDC138 (Proximity Label-MS), CCP110 (Proximity Label-MS), CEP152 (Proximity Label-MS), CEP170 (Proximity Label-MS)

ESM2 similar proteins: A0JMQ7, A1IH00, A2AUM9, D3YV10, G9G127, O94986, Q0VFN8, Q17QT2, Q2KJE0, Q3TDD9, Q3UKC1, Q3V6T2, Q5R4U3, Q5R5R4, Q5SNZ0, Q5T1M5, Q5TZ80, Q5U3A8, Q5ZJ27, Q5ZL12, Q5ZMV2, Q66HA4, Q66KE8, Q6GQ73, Q6IR70, Q6NRB0, Q6NRG6, Q6P132, Q6P3P1, Q6P9Q6, Q6UVJ0, Q6VGS5, Q6ZMI0, Q7ZVT3, Q80UF4, Q80UK7, Q80YF0, Q86VP1, Q86VS8, Q8BIL5

Diamond homologs: Q5ZMV2, Q6NRG6, Q6UVJ0, Q7ZVT3, Q80UK7

SIGNOR signaling

3 interactions.

A	Effect	B	Mechanism
NUP62	“up-regulates activity”	SASS6	binding
CEP135	“up-regulates activity”	SASS6	binding
FBXW5	“down-regulates quantity by destabilization”	SASS6	ubiquitination

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 83 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
AURKA Activation by TPX2	8	24.4×	3e-07
Loss of Nlp from mitotic centrosomes	7	22.2×	2e-06
Loss of proteins required for interphase microtubule organization from the centrosome	7	22.2×	2e-06
Recruitment of mitotic centrosome proteins and complexes	7	19.0×	5e-06
Regulation of PLK1 Activity at G2/M Transition	7	17.8×	7e-06
Recruitment of NuMA to mitotic centrosomes	7	16.3×	1e-05
Anchoring of the basal body to the plasma membrane	7	15.8×	1e-05

Disease & clinical

Clinical variants and AI predictions

ClinVar

157 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	3
Likely pathogenic	3
Uncertain significance	77
Likely benign	24
Benign	39

Top pathogenic / likely-pathogenic (6)

Variant ID	HGVS	Classification
192231	NM_194292.3(SASS6):c.185T>C (p.Ile62Thr)	Pathogenic
521498	NM_194292.3(SASS6):c.1186dup (p.Thr396fs)	Pathogenic
977772	NM_194292.3(SASS6):c.1867+2T>A	Pathogenic
2502836	NM_194292.3(SASS6):c.170del (p.Leu57fs)	Likely pathogenic
2506119	NM_194292.3(SASS6):c.497C>A (p.Ser166Ter)	Likely pathogenic
977344	NM_194292.3(SASS6):c.170dup (p.Leu57fs)	Likely pathogenic

SpliceAI

2218 predictions. Top by Δscore:

Variant	Effect	Δscore
1:100085628:CCA:C	acceptor_gain	1.0000
1:100085628:CCACT:C	acceptor_gain	1.0000
1:100085629:CA:C	acceptor_gain	1.0000
1:100085629:CAC:C	acceptor_gain	1.0000
1:100085630:ACT:A	acceptor_loss	1.0000
1:100085631:C:CA	acceptor_loss	1.0000
1:100085631:C:CC	acceptor_gain	1.0000
1:100085632:T:C	acceptor_gain	1.0000
1:100085632:T:TC	acceptor_gain	1.0000
1:100088137:A:AC	donor_gain	1.0000
1:100088138:C:CC	donor_gain	1.0000
1:100105899:GATTA:G	acceptor_gain	1.0000
1:100105901:TTA:T	acceptor_gain	1.0000
1:100105902:TA:T	acceptor_gain	1.0000
1:100105904:C:CC	acceptor_gain	1.0000
1:100105905:T:C	acceptor_gain	1.0000
1:100105905:T:TC	acceptor_gain	1.0000
1:100106906:A:AC	donor_gain	1.0000
1:100106906:ACT:A	donor_loss	1.0000
1:100106907:C:CC	donor_gain	1.0000
1:100106910:A:AC	donor_gain	1.0000
1:100106910:ACAC:A	donor_loss	1.0000
1:100106911:C:CC	donor_gain	1.0000
1:100106911:C:CG	donor_loss	1.0000
1:100106911:CA:C	donor_gain	1.0000
1:100106911:CACT:C	donor_gain	1.0000
1:100106911:CACTT:C	donor_gain	1.0000
1:100106991:TACC:T	acceptor_loss	1.0000
1:100106992:ACC:A	acceptor_loss	1.0000
1:100106994:C:CA	acceptor_loss	1.0000

AlphaMissense

4307 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:100121451:A:G	L137P	0.999
1:100122422:A:G	L90P	0.999
1:100107553:C:G	A383P	0.998
1:100107635:A:G	L380P	0.998
1:100107893:C:G	A325P	0.998
1:100121445:A:G	L139P	0.998
1:100121455:G:C	H136D	0.998
1:100121460:A:G	L134P	0.998
1:100122442:G:C	F83L	0.998
1:100122442:G:T	F83L	0.998
1:100122444:A:G	F83L	0.998
1:100122464:A:G	L76P	0.998
1:100123215:A:C	F67L	0.998
1:100123215:A:T	F67L	0.998
1:100123217:A:G	F67L	0.998
1:100123273:A:G	L48P	0.998
1:100105891:A:G	L474S	0.997
1:100107907:A:G	L320P	0.997
1:100121546:A:C	F105L	0.997
1:100121546:A:T	F105L	0.997
1:100121548:A:G	F105L	0.997
1:100122419:A:G	L91P	0.997
1:100122443:A:G	F83S	0.997
1:100123216:A:G	F67S	0.997
1:100107880:T:G	Q329P	0.996
1:100107967:C:G	R300P	0.996
1:100121453:G:C	H136Q	0.996
1:100121453:G:T	H136Q	0.996
1:100121468:A:C	F131L	0.996
1:100121468:A:T	F131L	0.996

dbSNP variants (sampled 300 via entrez): RS1000064848 (1:100115720 T>C), RS1000169963 (1:100100280 AAATG>A,AAATGAATG), RS1000278459 (1:100133107 G>A,C), RS1000336363 (1:100104382 T>A,G), RS1000414753 (1:100124341 A>C), RS1000472462 (1:100116310 A>G), RS1000490076 (1:100096755 T>C), RS1000600505 (1:100134133 A>C), RS1000612341 (1:100091953 A>G), RS1000622150 (1:100091587 G>A), RS1000628443 (1:100110001 T>A,C), RS1000689077 (1:100122357 T>C), RS1000772030 (1:100098720 T>C), RS1000867986 (1:100122276 G>T), RS1000916880 (1:100129394 G>C)

Disease associations

OMIM: gene MIM:609321 | disease phenotypes: MIM:616402

GenCC curated gene-disease

Disease	Classification	Inheritance
microcephaly 14, primary, autosomal recessive	Strong	Autosomal recessive
autosomal recessive primary microcephaly	Supportive	Autosomal recessive

Mondo (2): microcephaly 14, primary, autosomal recessive (MONDO:0014623), autosomal recessive primary microcephaly (MONDO:0016660)

Orphanet (1): Autosomal recessive primary microcephaly (Orphanet:2512)

HPO phenotypes

24 total (24 of 24 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000076	Vesicoureteral reflux
HP:0000122	Unilateral renal agenesis
HP:0000219	Thin upper lip vermilion
HP:0000252	Microcephaly
HP:0000340	Sloping forehead
HP:0000582	Upslanted palpebral fissure
HP:0000718	Aggressive behavior
HP:0001250	Seizure
HP:0001263	Global developmental delay
HP:0001274	Agenesis of corpus callosum
HP:0001302	Pachygyria
HP:0001320	Cerebellar vermis hypoplasia
HP:0001347	Hyperreflexia
HP:0001510	Growth delay
HP:0002119	Ventriculomegaly
HP:0002282	Gray matter heterotopia
HP:0002465	Poor speech
HP:0003103	Abnormal cortical bone morphology
HP:0003577	Congenital onset
HP:0004322	Short stature
HP:0007333	Hypoplasia of the frontal lobes
HP:0010864	Severe intellectual disability
HP:0011451	Primary microcephaly

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST012167_3	Adiponectin levels	2.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004502	adiponectin measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C579935	Autosomal Recessive Primary Microcephaly (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

39 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol A	increases expression, decreases expression	3
Acetaminophen	decreases expression, increases expression	2
Tetrachlorodibenzodioxin	decreases expression	2
Valproic Acid	decreases expression, decreases methylation, increases expression	2
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	2
aristolochic acid I	decreases expression	1
GSK-J4	increases expression	1
dicrotophos	decreases expression	1
triphenyl phosphate	affects expression	1
pirinixic acid	increases expression, affects binding, increases activity	1
arsenite	affects binding, decreases reaction	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
butyraldehyde	decreases expression	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
cupric oxide	decreases expression	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
CGP 52608	affects binding, increases reaction	1
jinfukang	decreases expression	1
incobotulinumtoxinA	decreases expression	1
(+)-JQ1 compound	decreases expression	1
Leflunomide	decreases expression	1
Air Pollutants	decreases expression, increases abundance	1
Calcitriol	affects cotreatment, decreases expression	1
Cisplatin	decreases expression	1
Dichlorodiphenyl Dichloroethylene	increases expression	1
Diethylstilbestrol	increases expression	1
Estradiol	increases expression	1
Formaldehyde	decreases expression	1
Oxygen	decreases expression	1
Quercetin	decreases expression	1

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.