SAMD3

Summary

SAMD3 (sterile alpha motif domain containing 3, HGNC:21574) is a protein-coding gene on chromosome 6q23.1, encoding Sterile alpha motif domain-containing protein 3 (Q8N6K7).

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 74 total
• MANE Select transcript: NM_001017373

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:21574
Approved symbol	SAMD3
Name	sterile alpha motif domain containing 3
Location	6q23.1
Locus type	gene with protein product
Status	Approved
Aliases	bA73O6.2, FLJ34032
Ensembl gene	ENSG00000164483
Ensembl biotype	protein_coding
OMIM	620516
Entrez	154075

Gene structure

Transcript identifiers

Ensembl transcripts: 15 — 10 protein_coding, 3 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay, 1 retained_intron

ENST00000324172, ENST00000368134, ENST00000437477, ENST00000439090, ENST00000457563, ENST00000463253, ENST00000524930, ENST00000526886, ENST00000528422, ENST00000529119, ENST00000529723, ENST00000531544, ENST00000532309, ENST00000532763, ENST00000533296

RefSeq mRNA: 3 — MANE Select: NM_001017373 NM_001017373, NM_001258275, NM_001277185

CCDS: CCDS34539, CCDS64525

Canonical transcript exons

ENST00000439090 — 12 exons

Exon	Start	End
ENSE00001404097	130222694	130222951
ENSE00001428487	130216571	130216616
ENSE00002142234	130145340	130145422
ENSE00002173990	130154825	130155025
ENSE00002195305	130146010	130146181
ENSE00002199723	130144315	130144804
ENSE00002200761	130175841	130176008
ENSE00003562331	130215195	130215294
ENSE00003574530	130184103	130184187
ENSE00003593740	130214337	130214526
ENSE00003623892	130184438	130184623
ENSE00003633038	130209495	130209608

Expression profiles

Bgee: expression breadth ubiquitous, 160 present calls, max score 97.92.

FANTOM5 (CAGE): breadth broad, TPM avg 5.1439 / max 430.5573, expressed in 457 samples.

FANTOM5 promoters (9 alternative TSS)

Promoter ID	TPM avg	Samples expressed
75521	1.5668	153
75524	1.4765	99
75522	1.1909	121
75530	0.3756	193
75525	0.1922	48
75526	0.1538	51
75529	0.0795	28
75523	0.0710	34
75528	0.0374	9

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
granulocyte	CL:0000094	97.92	gold quality
buccal mucosa cell	CL:0002336	89.44	gold quality
islet of Langerhans	UBERON:0000006	84.21	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	80.97	silver quality
spleen	UBERON:0002106	79.38	gold quality
lymph node	UBERON:0000029	78.03	gold quality
sural nerve	UBERON:0015488	76.91	gold quality
stromal cell of endometrium	CL:0002255	76.72	gold quality
bone marrow cell	CL:0002092	76.28	gold quality
blood	UBERON:0000178	76.26	gold quality
vermiform appendix	UBERON:0001154	76.02	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	75.81	gold quality
adrenal tissue	UBERON:0018303	75.73	gold quality
gall bladder	UBERON:0002110	74.18	gold quality
leukocyte	CL:0000738	73.93	gold quality
adenohypophysis	UBERON:0002196	73.27	gold quality
pituitary gland	UBERON:0000007	72.87	gold quality
body of uterus	UBERON:0009853	72.56	gold quality
rectum	UBERON:0001052	72.40	gold quality
right adrenal gland	UBERON:0001233	71.93	gold quality
right coronary artery	UBERON:0001625	71.92	gold quality
monocyte	CL:0000576	71.71	gold quality
calcaneal tendon	UBERON:0003701	71.67	gold quality
right adrenal gland cortex	UBERON:0035827	70.92	gold quality
left adrenal gland	UBERON:0001234	70.72	gold quality
colonic epithelium	UBERON:0000397	70.70	gold quality
upper lobe of left lung	UBERON:0008952	70.28	gold quality
left adrenal gland cortex	UBERON:0035825	70.26	gold quality
adrenal gland	UBERON:0002369	69.70	gold quality
smooth muscle tissue	UBERON:0001135	69.43	gold quality

Single-cell (SCXA)

Detected in 14 experiment(s), a significant marker in 13.

Experiment	Marker?	Max mean expression
E-CURD-112	yes	1255.49
E-MTAB-9388	yes	800.64
E-MTAB-6701	yes	106.22
E-MTAB-7008	yes	88.20
E-HCAD-1	yes	78.98
E-CURD-122	yes	49.23
E-MTAB-10287	yes	33.09
E-HCAD-10	yes	32.83
E-MTAB-6678	yes	25.88
E-ANND-3	yes	15.22
E-MTAB-10553	yes	11.11
E-MTAB-9067	yes	4.94
E-GEOD-130148	yes	3.58
E-MTAB-7606	no	504.03

Regulation

Is transcription factor: no

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
mus_musculus	Samd3	ENSMUSG00000051354
rattus_norvegicus	Samd3	ENSRNOG00000039955
drosophila_melanogaster	cnk	FBGN0286070
caenorhabditis_elegans		WBGENE00000564

Paralogs (4): IPCEF1 (ENSG00000074706), CNKSR1 (ENSG00000142675), CNKSR2 (ENSG00000149970), CNKSR3 (ENSG00000153721)

Protein

Protein identifiers

Sterile alpha motif domain-containing protein 3 — Q8N6K7 (reviewed: Q8N6K7)

All UniProt accessions (7): E9PPN0, E9PR28, E9PR45, E9PRU9, Q8N6K7, E9PS85, H0YEH9

Isoforms (3)

UniProt ID	Names	Canonical?
Q8N6K7-1	1	yes
Q8N6K7-2	2
Q8N6K7-3	3

RefSeq proteins (3): NP_001017373, NP_001245204, NP_001264114 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001660	SAM	Domain
IPR013761	SAM/pointed_sf	Homologous_superfamily
IPR042812	SAMD3	Family
IPR042813	SAMD3_SAM	Domain

Pfam: PF00536

UniProt features (10 total): splice variant 3, sequence variant 2, sequence conflict 2, chain 1, domain 1, region of interest 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8N6K7-F1	76.70	0.42

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 71 (showing top): GSE45365_HEALTHY_VS_MCMV_INFECTION_CD8_TCELL_IFNAR_KO_DN, GSE45365_NK_CELL_VS_CD8_TCELL_DN, HP1SITEFACTOR_Q6, LEE_EARLY_T_LYMPHOCYTE_DN, ARGGGTTAA_UNKNOWN, ZHAN_MULTIPLE_MYELOMA_LB_UP, GEORGES_TARGETS_OF_MIR192_AND_MIR215, chr6q23, BOSCO_TH1_CYTOTOXIC_MODULE, GSE14415_INDUCED_TREG_VS_FOXP3_KO_INDUCED_TREG_DN, GSE14415_INDUCED_TREG_VS_FOXP3_KO_INDUCED_TREG_IL2_CULTURE_UP, GSE14415_INDUCED_TREG_VS_TCONV_DN, GSE14415_ACT_VS_CTRL_NATURAL_TREG_DN, GSE14415_INDUCED_VS_NATURAL_TREG_UP, GSE14415_NATURAL_TREG_VS_FOXP3_KO_NATURAL_TREG_DN

GO Biological Process (0):

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

GO Cellular Component (0):

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
binding	1

Protein interactions and networks

STRING

540 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SAMD3	SMAD2	Q15796	668
SAMD3	SMAD4	Q13485	636
SAMD3	SMAD3	P84022	620
SAMD3	RNF157	Q96PX1	450
SAMD3	AKT1	P31749	445
SAMD3	TGFB1	P01137	420
SAMD3	TMEM200A	Q86VY9	418
SAMD3	UNC45B	Q8IWX7	404
SAMD3	MAPK8	P45983	398
SAMD3	CREBBP	Q92793	394
SAMD3	RUNX1	Q01196	394
SAMD3	RARA	P10276	386
SAMD3	BTRC	Q9Y297	385
SAMD3	DNAAF4	Q8WXU2	374
SAMD3	NCOA3	Q9Y6Q9	374

IntAct

20 interactions, top by confidence:

A	B	Type	Score
HSPD1	SAMD3	psi-mi:“MI:0915”(physical association)	0.670
SAMD3	HSPD1	psi-mi:“MI:0915”(physical association)	0.670
SAMD3	CFAP206	psi-mi:“MI:0915”(physical association)	0.560
SAMD3	LMO3	psi-mi:“MI:0915”(physical association)	0.560
AKAP9	SAMD3	psi-mi:“MI:0915”(physical association)	0.560
CFAP206	SAMD3	psi-mi:“MI:0915”(physical association)	0.560
LMO3	SAMD3	psi-mi:“MI:0915”(physical association)	0.560
SAMD3	KDM1A	psi-mi:“MI:0915”(physical association)	0.510
SAMD3	CFTR	psi-mi:“MI:0915”(physical association)	0.370
FANCG	SAMD3	psi-mi:“MI:0915”(physical association)	0.370
SAMD3	PRMT1	psi-mi:“MI:0915”(physical association)	0.370
SAMD3	MYO9A	psi-mi:“MI:0914”(association)	0.350

BioGRID (18): SAMD3 (Two-hybrid), SAMD3 (Two-hybrid), SAMD3 (Two-hybrid), C6orf165 (Two-hybrid), SAMD3 (Two-hybrid), SAMD3 (Two-hybrid), SAMD3 (Two-hybrid), SAMD3 (Affinity Capture-MS), HERC2 (Affinity Capture-MS), MYO9A (Affinity Capture-MS), NEURL4 (Affinity Capture-MS), ACACB (Affinity Capture-MS), TRIM7 (Affinity Capture-MS), SUGP2 (Affinity Capture-MS), SAMD3 (PCA)

ESM2 similar proteins: A0A8I3NFE2, A0JM59, A2RT67, A5PK16, A5PN09, A7Z056, D3YZI9, D7PF45, F1QGZ6, O14757, O15357, O35710, O81360, P36195, P41002, P51944, Q0JCU7, Q32NJ2, Q32NM1, Q5E9N5, Q5F3G0, Q5R5Z6, Q5T447, Q5XGG5, Q6DI92, Q6P549, Q6ZN16, Q7T0L6, Q7TN16, Q7ZUM8, Q80TA6, Q80WG7, Q8AYC9, Q8BRH3, Q8C6M1, Q8K4F8, Q8N414, Q8N6K7, Q8W519, Q94K49

Diamond homologs: Q8C4H2, Q8N6K7

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	63
Likely benign	4
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

3467 predictions. Top by Δscore:

Variant	Effect	Δscore
6:130145335:CATA:C	donor_loss	1.0000
6:130145336:ATACC:A	donor_loss	1.0000
6:130145337:TACCT:T	donor_loss	1.0000
6:130145338:A:C	donor_loss	1.0000
6:130145421:GT:G	acceptor_gain	1.0000
6:130145422:TCTG:T	acceptor_loss	1.0000
6:130145423:C:CC	acceptor_gain	1.0000
6:130146008:A:AC	donor_gain	1.0000
6:130146009:C:CC	donor_gain	1.0000
6:130146009:CATTT:C	donor_gain	1.0000
6:130154820:GATAC:G	donor_loss	1.0000
6:130154822:TACC:T	donor_loss	1.0000
6:130154823:AC:A	donor_loss	1.0000
6:130154824:CCT:C	donor_loss	1.0000
6:130154865:T:TA	donor_gain	1.0000
6:130155026:CT:C	acceptor_loss	1.0000
6:130155027:T:G	acceptor_loss	1.0000
6:130175839:A:AC	donor_gain	1.0000
6:130175840:C:CC	donor_gain	1.0000
6:130175891:T:A	donor_gain	1.0000
6:130176004:AAAAA:A	acceptor_gain	1.0000
6:130176005:AAAA:A	acceptor_gain	1.0000
6:130176006:AAA:A	acceptor_gain	1.0000
6:130176006:AAAC:A	acceptor_loss	1.0000
6:130176007:AA:A	acceptor_gain	1.0000
6:130176007:AAC:A	acceptor_loss	1.0000
6:130176009:C:A	acceptor_loss	1.0000
6:130176009:C:CC	acceptor_gain	1.0000
6:130176010:T:G	acceptor_loss	1.0000
6:130176011:G:C	acceptor_gain	1.0000

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000028960 (6:130349550 A>T), RS1000039284 (6:130146115 A>C,G), RS1000041410 (6:130175264 C>T), RS1000045851 (6:130259559 A>G), RS1000048647 (6:130238127 T>C), RS1000055372 (6:130171857 G>A,T), RS1000082167 (6:130349292 T>C), RS1000103520 (6:130253087 A>G), RS1000116476 (6:130268500 C>CCACT), RS1000135352 (6:130328137 C>A), RS1000159592 (6:130229247 G>C), RS1000180413 (6:130331485 G>A), RS1000193216 (6:130152212 C>G), RS1000245466 (6:130151836 A>G), RS1000256248 (6:130192010 C>G)

Disease associations

OMIM: gene MIM:620516 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST000175_31	Height	6.000000e-06
GCST003142_4	Proteinuria in chronic kidney disease	9.000000e-06
GCST004863_88	Mosquito bite size	4.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0008378	mosquito bite reaction size measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

19 total (human), top 19 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	decreases expression, increases expression, increases methylation	3
triphenyl phosphate	affects expression	1
bisphenol A	affects cotreatment, increases methylation	1
2,5,2’,5’-tetrachlorobiphenyl	decreases expression	1
trichostatin A	increases expression	1
benzo(e)pyrene	decreases methylation	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	affects binding, increases reaction	1
bisphenol S	decreases expression	1
(+)-JQ1 compound	decreases expression	1
Fulvestrant	affects cotreatment, increases methylation	1
Arsenic	affects methylation	1
Diethylhexyl Phthalate	increases expression	1
Methapyrilene	decreases methylation	1
Nickel	increases expression	1
Valproic Acid	affects expression	1
8-Bromo Cyclic Adenosine Monophosphate	decreases expression	1
Aflatoxin B1	affects methylation	1
Antirheumatic Agents	decreases expression	1

Clinical trials (associated diseases)

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