SAC3D1

Summary

SAC3D1 (SAC3 domain containing 1, HGNC:30179) is a protein-coding gene on chromosome 11q13.1, encoding SAC3 domain-containing protein 1 (A6NKF1). Involved in centrosome duplication and mitotic progression.

Predicted to be involved in centrosome duplication and spindle assembly. Predicted to act upstream of or within negative regulation of receptor signaling pathway via JAK-STAT and regulation of immune response. Predicted to be located in microtubule cytoskeleton. Predicted to be part of protein-containing complex. Predicted to be active in centrosome; nucleus; and spindle.

Source: NCBI Gene 29901 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 44 total
• MANE Select transcript: NM_013299

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:30179
Approved symbol	SAC3D1
Name	SAC3 domain containing 1
Location	11q13.1
Locus type	gene with protein product
Status	Approved
Aliases	HSU79266, SHD1
Ensembl gene	ENSG00000168061
Ensembl biotype	protein_coding
OMIM	618796
Entrez	29901

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 4 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000398846, ENST00000531072, ENST00000533017, ENST00000652489, ENST00000674184

RefSeq mRNA: 5 — MANE Select: NM_013299 NM_001367485, NM_001367486, NM_001367487, NM_001367488, NM_013299

CCDS: CCDS41668, CCDS91505, CCDS91506

Canonical transcript exons

ENST00000652489 — 2 exons

Exon	Start	End
ENSE00002153784	65044225	65044828
ENSE00003850216	65041210	65041866

Expression profiles

Bgee: expression breadth ubiquitous, 246 present calls, max score 94.20.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 10.3592 / max 50.0734, expressed in 1710 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
115019	6.6564	1560
115016	2.8409	1449
115020	0.6019	379
115018	0.2512	82
115017	0.0087	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
endometrium epithelium	UBERON:0004811	94.20	gold quality
right testis	UBERON:0004534	91.90	gold quality
left testis	UBERON:0004533	91.83	gold quality
tendon of biceps brachii	UBERON:0008188	91.42	silver quality
gingival epithelium	UBERON:0001949	91.02	gold quality
sperm	CL:0000019	90.60	gold quality
testis	UBERON:0000473	90.48	gold quality
mucosa of transverse colon	UBERON:0004991	89.00	gold quality
male germ cell	CL:0000015	88.95	silver quality
gingiva	UBERON:0001828	88.69	gold quality
medial globus pallidus	UBERON:0002477	87.74	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	87.23	gold quality
amniotic fluid	UBERON:0000173	87.12	gold quality
palpebral conjunctiva	UBERON:0001812	86.42	gold quality
cervix squamous epithelium	UBERON:0006922	86.34	silver quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	86.22	gold quality
adult organism	UBERON:0007023	85.71	gold quality
squamous epithelium	UBERON:0006914	84.76	gold quality
Brodmann (1909) area 23	UBERON:0013554	83.69	gold quality
hindlimb stylopod muscle	UBERON:0004252	83.61	gold quality
esophagus squamous epithelium	UBERON:0006920	83.15	gold quality
thymus	UBERON:0002370	83.10	silver quality
ganglionic eminence	UBERON:0004023	82.76	gold quality
globus pallidus	UBERON:0001875	82.66	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	82.15	silver quality
tibia	UBERON:0000979	82.09	gold quality
gastrocnemius	UBERON:0001388	81.88	gold quality
epithelium of esophagus	UBERON:0001976	81.75	gold quality
parotid gland	UBERON:0001831	81.65	gold quality
right hemisphere of cerebellum	UBERON:0014890	81.55	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-CURD-88	no	3.80
E-ANND-3	no	2.68

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

5 targeting SAC3D1, 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-4283	100.00	66.42	2097
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-302E	99.96	70.74	2669
HSA-MIR-7153-3P	99.00	65.35	608
HSA-MIR-619-3P	98.38	65.58	693

Literature-anchored findings (GeneRIF, showing 5)

• SHD1 is a novel cytokine-inducible negative feedback regulator of STAT5a. (PMID:18838617)
• In this study, 3 independent cohorts (GSE10186, n = 80; TCGA, n = 330 and ICGC, n = 237) were used to assess SAC3D1 as a biomarker, which demonstrated SAC3D1 overexpression in hepatocellular carcinoma tissues when compared to the matched normal tissues. (PMID:30353105)
• Distinct effects on mRNA export factor GANP underlie neurological disease phenotypes and alter gene expression depending on intron content. (PMID:32202298)
• Upregulated expression of SAC3D1 is associated with progression in gastric cancer. (PMID:32319600)
• SAC3D1 activates Wnt/betacatenin signalling in hepatocellular carcinoma. (PMID:36004462)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	sac3d1	ENSDARG00000071271
mus_musculus	Sac3d1	ENSMUSG00000024790
rattus_norvegicus	Sac3d1	ENSRNOG00000021003
drosophila_melanogaster	CG3437	FBGN0035998
caenorhabditis_elegans		WBGENE00006466

Paralogs (2): MCM3AP (ENSG00000160294), LENG8 (ENSG00000167615)

Protein

Protein identifiers

SAC3 domain-containing protein 1 — A6NKF1 (reviewed: A6NKF1)

Alternative names: SAC3 homology domain-containing protein 1

All UniProt accessions (3): A0A6I8PRW4, F8WC89, H9KVA8

UniProt curated annotations — full annotation on UniProt →

Function. Involved in centrosome duplication and mitotic progression.

Subunit / interactions. May be part of a SEM1-containing complex.

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

Polymorphism. A single nucleotide deletion in the N-terminal region of the protein leads to production of a shorter protein starting at Met-47 which matches the reference genome (GRCh38/hg38) but is likely to be the minor allele.

Similarity. Belongs to the SAC3 family.

Isoforms (2)

UniProt ID	Names	Canonical?
A6NKF1-1	1	yes
A6NKF1-2	2

RefSeq proteins (5): NP_001354414, NP_001354415, NP_001354416, NP_001354417, NP_037431* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000717	PCI_dom	Domain
IPR005062	SAC3/GANP/THP3_conserved	Domain
IPR045107	SAC3/GANP/THP3	Family

Pfam: PF03399

UniProt features (12 total): sequence variant 3, region of interest 2, compositionally biased region 2, chain 1, domain 1, sequence conflict 1, modified residue 1, splice variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-A6NKF1-F1	83.66	0.67

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 (1): 402

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 173 (showing top): BUYTAERT_PHOTODYNAMIC_THERAPY_STRESS_DN, YAGI_AML_WITH_INV_16_TRANSLOCATION, STARK_PREFRONTAL_CORTEX_22Q11_DELETION_DN, MATTIOLI_MGUS_VS_PCL, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_UP, DACOSTA_UV_RESPONSE_VIA_ERCC3_UP, chr11q13, GOCC_MICROTUBULE_ORGANIZING_CENTER, PATIL_LIVER_CANCER, GROSS_HYPOXIA_VIA_ELK3_UP, BILD_E2F3_ONCOGENIC_SIGNATURE, GROSS_HYPOXIA_VIA_ELK3_AND_HIF1A_DN, GOCC_CENTROSOME, GOBP_ORGANELLE_ASSEMBLY

GO Biological Process (3): spindle assembly (GO:0051225), centrosome duplication (GO:0051298), cell division (GO:0051301)

GO Molecular Function (0):

GO Cellular Component (4): nucleus (GO:0005634), centrosome (GO:0005813), spindle (GO:0005819), protein-containing complex (GO:0032991)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
spindle organization	1
chromosome segregation	1
membraneless organelle assembly	1
centrosome cycle	1
cell cycle process	1
cellular process	1
intracellular membrane-bounded organelle	1
centriole	1
microtubule organizing center	1
microtubule cytoskeleton	1
intracellular membraneless organelle	1
cellular_component	1

Protein interactions and networks

STRING

1006 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SAC3D1	TMEM160	Q9NX00	543
SAC3D1	PKMYT1	Q99640	460
SAC3D1	ARHGEF6	Q15052	458
SAC3D1	CCDC167	Q9P0B6	427
SAC3D1	PPM1G	O15355	418
SAC3D1	SKA2	Q8WVK7	398
SAC3D1	SLA	Q13239	397
SAC3D1	ZMYND19	Q96E35	396
SAC3D1	RAD54L	Q92698	380
SAC3D1	RRS1	Q15050	364
SAC3D1	SYTL1	Q8IYJ3	359
SAC3D1	MCM2	P49736	353
SAC3D1	ENY2	Q9NPA8	349
SAC3D1	CCDC34	Q96HJ3	346
SAC3D1	PCID2	Q5JVF3	332

IntAct

10 interactions, top by confidence:

A	B	Type	Score
NS1		psi-mi:“MI:0914”(association)	0.350
NS1	SAC3D1	psi-mi:“MI:0914”(association)	0.350
NS1	ESYT2	psi-mi:“MI:0914”(association)	0.350
PRSS33	SAC3D1	psi-mi:“MI:0914”(association)	0.350

ESM2 similar proteins: A3KN25, A6H687, A6NE52, A6NKF1, A6QQ91, A8MYJ7, D2HS90, E1BD59, O08580, O09017, O75064, O75427, O94812, P0C5W1, P11474, P43136, P52824, P58660, Q08DF2, Q08DM2, Q1JPD6, Q2TBW5, Q3U0S6, Q3U1Y4, Q562E7, Q5BK61, Q5JR98, Q5JZY3, Q5QJV7, Q5U651, Q6F5E8, Q6QMY5, Q86YV0, Q8BYG9, Q8C052, Q8C2K5, Q8CDY7, Q8R5G7, Q8WWN8, Q96HA7

Diamond homologs: A6H687, A6NKF1, O60318, Q9USI4, Q9WUU9, F4JAU2, O74889, Q67XV2, Q9U3V9, P46674, Q1MTP1

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	39
Likely benign	4
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

474 predictions. Top by Δscore:

Variant	Effect	Δscore
11:65044223:A:AG	acceptor_gain	1.0000
11:65044224:G:GG	acceptor_gain	1.0000
11:65041865:GG:G	donor_gain	0.9900
11:65041866:GG:G	donor_gain	0.9900
11:65044214:C:A	acceptor_gain	0.9900
11:65044220:CACA:C	acceptor_loss	0.9900
11:65044222:CAGGC:C	acceptor_loss	0.9900
11:65044223:AG:A	acceptor_gain	0.9900
11:65044223:AGG:A	acceptor_loss	0.9900
11:65044224:G:GC	acceptor_loss	0.9900
11:65044224:GG:G	acceptor_gain	0.9900
11:65044224:GGC:G	acceptor_gain	0.9900
11:65044224:GGCT:G	acceptor_gain	0.9900
11:65044224:GGCTC:G	acceptor_gain	0.9900
11:65041770:G:GT	donor_gain	0.9700
11:65041864:TGGGT:T	donor_loss	0.9700
11:65041865:GGGT:G	donor_loss	0.9700
11:65041868:T:TC	donor_loss	0.9700
11:65041869:G:GT	donor_loss	0.9700
11:65044221:A:AG	acceptor_gain	0.9700
11:65041699:T:TA	donor_gain	0.9600
11:65041700:A:AA	donor_gain	0.9600
11:65041862:CCTGG:C	donor_gain	0.9600
11:65041867:G:GG	donor_gain	0.9600
11:65041870:AGT:A	donor_loss	0.9600
11:65044221:ACAG:A	acceptor_gain	0.9600
11:65041766:GC:G	donor_gain	0.9400
11:65041871:G:C	donor_loss	0.9400
11:65041765:TGC:T	donor_gain	0.9300
11:65041863:CTGG:C	donor_gain	0.9300

AlphaMissense

2244 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000145233 (11:65040295 G>A), RS1000788110 (11:65041586 C>G,T), RS1001296983 (11:65039539 T>C,G), RS1001328180 (11:65038981 T>C), RS1002144533 (11:65042461 C>G,T), RS1002900574 (11:65043981 C>T), RS1003642011 (11:65040877 C>T), RS1003811076 (11:65043964 C>T), RS1005792808 (11:65040923 C>A), RS1006094168 (11:65041069 A>G), RS1006155299 (11:65045295 G>A,C), RS1006901497 (11:65041226 G>C), RS1007014617 (11:65040500 G>A), RS1008126111 (11:65042686 C>T), RS1008666712 (11:65042961 A>G)

Disease associations

OMIM: gene MIM:618796 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	increases expression, decreases expression	3
Particulate Matter	increases expression, decreases expression, increases abundance, affects cotreatment	3
Resveratrol	affects cotreatment, increases expression, decreases expression	2
Air Pollutants	decreases expression, increases abundance	2
Benzo(a)pyrene	increases expression, increases methylation	2
Cisplatin	increases expression	2
Valproic Acid	increases expression, increases methylation	2
aristolochic acid I	increases expression	1
FR900359	increases phosphorylation	1
bisphenol F	affects cotreatment, increases expression	1
bisphenol A	increases expression	1
beta-lapachone	decreases expression	1
arsenite	affects binding, increases reaction	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
perfluorooctanoic acid	decreases expression	1
coumarin	increases phosphorylation	1
di-n-butylphosphoric acid	affects expression	1
K 7174	decreases expression	1
abrine	decreases expression	1
(4-amino-1,4-dihydro-3-(2-pyridyl)-5-thioxo-1,2,4-triazole)copper(II)	decreases expression	1
2-(1H-indazol-4-yl)-6-(4-methanesulfonylpiperazin-1-ylmethyl)-4-morpholin-4-ylthieno(3,2-d)pyrimidine	decreases expression, increases response to substance	1
NSC 689534	affects binding, decreases expression	1
Adenine	decreases expression	1
Ethanol	affects cotreatment, increases abundance, increases expression	1
Cadmium	increases expression	1
Colchicine	decreases expression	1
Copper	affects binding, decreases expression	1
Coumestrol	affects cotreatment, increases expression	1
Dichlorodiphenyl Dichloroethylene	increases expression	1
Dexamethasone	affects cotreatment, increases expression	1

Clinical trials (associated diseases)

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