SAMD5

Summary

SAMD5 (sterile alpha motif domain containing 5, HGNC:21180) is a protein-coding gene on chromosome 6q24.3, encoding Sterile alpha motif domain-containing protein 5 (Q5TGI4).

Predicted to be involved in regulation of intracellular signal transduction. Located in cytoplasm.

Source: NCBI Gene 389432 — RefSeq curated summary.

At a glance

• GWAS associations: 9
• Clinical variants (ClinVar): 38 total
• MANE Select transcript: NM_001030060

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:21180
Approved symbol	SAMD5
Name	sterile alpha motif domain containing 5
Location	6q24.3
Locus type	gene with protein product
Status	Approved
Aliases	dJ875H10.1
Ensembl gene	ENSG00000203727
Ensembl biotype	protein_coding
OMIM	620517
Entrez	389432

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 2 protein_coding

ENST00000367474, ENST00000566741

RefSeq mRNA: 1 — MANE Select: NM_001030060 NM_001030060

CCDS: CCDS34548

Canonical transcript exons

ENST00000367474 — 2 exons

Exon	Start	End
ENSE00001444603	147564394	147570021
ENSE00001444606	147508690	147509387

Expression profiles

Bgee: expression breadth ubiquitous, 201 present calls, max score 92.24.

FANTOM5 (CAGE): breadth broad, TPM avg 4.3700 / max 140.0441, expressed in 741 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
70398	3.8301	718
70399	0.3694	206
70397	0.1706	86

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
kidney epithelium	UBERON:0004819	92.24	gold quality
esophagus squamous epithelium	UBERON:0006920	91.36	gold quality
mammary duct	UBERON:0001765	87.06	gold quality
epithelium of mammary gland	UBERON:0003244	87.00	gold quality
mucosa of sigmoid colon	UBERON:0004993	85.80	gold quality
colonic mucosa	UBERON:0000317	83.83	gold quality
visceral pleura	UBERON:0002401	83.49	gold quality
epithelial cell of pancreas	CL:0000083	82.06	silver quality
buccal mucosa cell	CL:0002336	81.63	gold quality
placenta	UBERON:0001987	81.03	gold quality
islet of Langerhans	UBERON:0000006	80.98	gold quality
ileal mucosa	UBERON:0000331	80.67	gold quality
cauda epididymis	UBERON:0004360	79.49	gold quality
lower esophagus mucosa	UBERON:0035834	79.27	gold quality
rectum	UBERON:0001052	79.25	gold quality
adult mammalian kidney	UBERON:0000082	79.24	gold quality
mammary gland	UBERON:0001911	78.80	gold quality
thoracic mammary gland	UBERON:0005200	78.65	gold quality
oral cavity	UBERON:0000167	78.18	gold quality
kidney	UBERON:0002113	78.09	gold quality
pigmented layer of retina	UBERON:0001782	77.75	gold quality
esophagus mucosa	UBERON:0002469	77.57	gold quality
lower lobe of lung	UBERON:0008949	77.23	gold quality
liver	UBERON:0002107	77.04	gold quality
right lobe of liver	UBERON:0001114	76.79	gold quality
gingiva	UBERON:0001828	76.34	gold quality
gingival epithelium	UBERON:0001949	75.51	silver quality
colonic epithelium	UBERON:0000397	75.32	gold quality
germinal epithelium of ovary	UBERON:0001304	75.01	silver quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	74.85	silver quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-GEOD-81608	yes	8.16
E-ANND-3	yes	5.68
E-MTAB-6058	no	35.74

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): EGR4

miRNA regulators (miRDB)

165 targeting SAMD5, 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-5692A	100.00	74.40	6850
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-4455	100.00	65.48	1587
HSA-MIR-3924	100.00	72.09	2394
HSA-MIR-568	99.98	69.86	2084
HSA-LET-7F-2-3P	99.98	70.98	2588
HSA-MIR-1185-1-3P	99.98	71.04	2593
HSA-MIR-1185-2-3P	99.98	71.04	2593
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-9-3P	99.96	70.88	2068
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-4760-3P	99.93	70.50	2385
HSA-MIR-3682-5P	99.93	67.97	1163
HSA-MIR-3143	99.93	71.96	3104
HSA-MIR-6835-3P	99.93	70.49	2904
HSA-MIR-4778-3P	99.93	70.40	1818
HSA-MIR-3119	99.92	71.34	2390
HSA-MIR-450B-5P	99.92	71.48	3175
HSA-MIR-6809-3P	99.91	71.45	3814
HSA-MIR-1305	99.91	71.43	3443
HSA-MIR-10527-5P	99.91	72.28	3754
HSA-MIR-498-3P	99.91	71.27	1114

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	SAMD5	ENSDARG00000110032
mus_musculus	Samd5	ENSMUSG00000060487
rattus_norvegicus	Samd5	ENSRNOG00000023549

Protein

Protein identifiers

Sterile alpha motif domain-containing protein 5 — Q5TGI4 (reviewed: Q5TGI4)

All UniProt accessions (2): Q5TGI4, H3BS43

UniProt curated annotations — full annotation on UniProt →

Subunit / interactions. Interacts promiscuously (via SAM domain) with EPHA5, EPHA6, EPHA7, EPHA8, EPHB1, EPHB2, EPHB3 and EPHB4 (via SAM domain) (in vitro).

Subcellular location. Cytoplasm.

Tissue specificity. Detected in biliary epithelial cells on bile ducts at the hepatic hilum (at protein level).

RefSeq proteins (1): NP_001025231* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001660	SAM	Domain
IPR013761	SAM/pointed_sf	Homologous_superfamily
IPR051725	SAM-SH3_domain_protein	Family

Pfam: PF00536

UniProt features (4 total): chain 1, domain 1, region of interest 1, compositionally biased region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q5TGI4-F1	71.96	0.35

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 84 (showing top): GSE18804_SPLEEN_MACROPHAGE_VS_BRAIN_TUMORAL_MACROPHAGE_UP, GSE18804_SPLEEN_MACROPHAGE_VS_TUMORAL_MACROPHAGE_UP, GSE18804_BRAIN_VS_COLON_TUMORAL_MACROPHAGE_UP, STARK_PREFRONTAL_CORTEX_22Q11_DELETION_DN, DAWSON_METHYLATED_IN_LYMPHOMA_TCL1, SCHAEFFER_PROSTATE_DEVELOPMENT_6HR_DN, SCHAEFFER_PROSTATE_DEVELOPMENT_48HR_DN, GARCIA_TARGETS_OF_FLI1_AND_DAX1_DN, GGCAGTG_MIR3243P, TURASHVILI_BREAST_DUCTAL_CARCINOMA_VS_DUCTAL_NORMAL_DN, RIGGI_EWING_SARCOMA_PROGENITOR_UP, WANG_SMARCE1_TARGETS_UP, VECCHI_GASTRIC_CANCER_EARLY_UP, GSE13762_CTRL_VS_125_VITAMIND_DAY5_DC_UP, GABRIELY_MIR21_TARGETS

GO Biological Process (1): regulation of intracellular signal transduction (GO:1902531)

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

GO Cellular Component (2): cytoplasm (GO:0005737), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
regulation of signal transduction	1
intracellular signal transduction	1
binding	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

508 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SAMD5	LRRIQ3	A6PVS8	670
SAMD5	FRMD3	A2A2Y4	616
SAMD5	TMC7	Q7Z402	572
SAMD5	SAMD10	Q9BYL1	516
SAMD5	SASH1	O94885	478
SAMD5	STXBP5	Q5T5C0	472
SAMD5	SAMD14	Q8IZD0	472
SAMD5	ADGB	Q8N7X0	470
SAMD5	CALY	Q9NYX4	430
SAMD5	EPHB1	P54762	405
SAMD5	EPHA8	P29322	396
SAMD5	A0A024R161	A0A024R161	391
SAMD5	SAMD7	Q7Z3H4	387
SAMD5	KBTBD6	Q86V97	375
SAMD5	SAMD3	Q8N6K7	350

IntAct

0 interactions, top by confidence:

BioGRID (1): SAMD5 (Affinity Capture-MS)

ESM2 similar proteins: A4FV57, A6H7I8, B2RYF1, D3YYI7, G3V9M2, M0R7T9, O08838, O09112, O43189, O60347, O94827, P49418, P49797, Q09YL6, Q0IHY4, Q13202, Q13387, Q147X3, Q3TZ87, Q3V038, Q3V1H9, Q5CD77, Q5RD33, Q5TGI4, Q5VV17, Q5XI70, Q66T02, Q6A039, Q6ZN18, Q70EL4, Q7Z6G3, Q7Z6J2, Q80UW0, Q86YJ5, Q8BKR5, Q8C4U2, Q8CE64, Q8CGA2, Q8N554, Q8TBP0

Diamond homologs: A0A8I3NFE2, A0FI79, A0JNB0, A1Y2K1, A6QLK6, B2RZ59, B5KFD7, D3ZGS3, D7PF45, F1RDG9, G5ECJ6, O14306, O14796, O15357, O35324, O60880, O88890, O88900, P00519, P00520, P00521, P00522, P03949, P06239, P06241, P09851, P0CE43, P10447, P17713, P20936, P29350, P29351, P32019, P34370, P39688, P42684, P42685, P42686, P50904, P53356

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	34
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

987 predictions. Top by Δscore:

Variant	Effect	Δscore
6:147562369:G:GT	donor_gain	1.0000
6:147509383:GCAAG:G	donor_gain	0.9900
6:147509388:G:GG	donor_gain	0.9900
6:147509333:GGA:G	donor_gain	0.9800
6:147529704:G:GG	donor_gain	0.9800
6:147562373:T:TA	donor_gain	0.9800
6:147562374:A:AA	donor_gain	0.9800
6:147564512:GGCA:G	donor_gain	0.9800
6:147509386:AG:A	donor_gain	0.9700
6:147509387:GG:G	donor_gain	0.9700
6:147509393:G:GT	donor_gain	0.9700
6:147564541:G:T	donor_gain	0.9600
6:147561884:TCATG:T	donor_gain	0.9500
6:147562369:G:T	donor_gain	0.9500
6:147529703:A:AG	donor_gain	0.9400
6:147529700:C:G	donor_gain	0.9300
6:147530237:G:C	acceptor_gain	0.9300
6:147561774:A:AG	acceptor_gain	0.9300
6:147569873:A:AG	acceptor_gain	0.9300
6:147569874:G:GG	acceptor_gain	0.9300
6:147569398:C:G	donor_gain	0.9200
6:147529648:A:AG	donor_gain	0.9100
6:147529649:G:GG	donor_gain	0.9100
6:147529700:C:CG	donor_gain	0.9100
6:147568110:T:G	acceptor_gain	0.9100
6:147525904:G:GA	donor_gain	0.8700
6:147559591:G:GT	donor_gain	0.8700
6:147561775:CTTGA:C	acceptor_gain	0.8400
6:147569874:GTT:G	acceptor_gain	0.8400
6:147561775:C:G	acceptor_gain	0.8300

AlphaMissense

1110 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:147508953:T:A	W9R	1.000
6:147508953:T:C	W9R	1.000
6:147508955:G:C	W9C	1.000
6:147508955:G:T	W9C	1.000
6:147508957:T:C	L10P	1.000
6:147508993:T:C	F22S	1.000
6:147509003:C:A	N25K	1.000
6:147509003:C:G	N25K	1.000
6:147509005:G:A	G26D	1.000
6:147509005:G:T	G26V	1.000
6:147509007:T:C	Y27H	1.000
6:147509025:T:C	C33R	1.000
6:147509026:G:A	C33Y	1.000
6:147509027:C:G	C33W	1.000
6:147509030:G:C	K34N	1.000
6:147509030:G:T	K34N	1.000
6:147509050:T:C	L41P	1.000
6:147509317:T:C	L130P	1.000
6:147508945:T:A	V6D	0.999
6:147508954:G:C	W9S	0.999
6:147508957:T:A	L10H	0.999
6:147508972:T:C	L15P	0.999
6:147508993:T:G	F22C	0.999
6:147509002:A:T	N25I	0.999
6:147509004:G:C	G26R	0.999
6:147509004:G:T	G26C	0.999
6:147509007:T:A	Y27N	0.999
6:147509007:T:G	Y27D	0.999
6:147509008:A:C	Y27S	0.999
6:147509035:T:A	I36N	0.999

dbSNP variants (sampled 300 via entrez): RS1000010602 (6:147914590 C>T), RS1000015044 (6:147907735 C>T), RS1000031332 (6:147610371 G>A), RS1000039035 (6:147510349 G>A,C), RS1000040055 (6:147947680 T>C), RS1000083648 (6:147588744 C>T), RS1000084710 (6:147595959 C>G), RS1000099018 (6:147788944 C>T), RS1000113152 (6:147593532 G>A), RS1000114935 (6:147696459 C>T), RS1000124497 (6:147658418 T>C,G), RS1000131667 (6:147654440 A>C,G), RS1000132776 (6:147809699 T>C), RS1000137339 (6:147943868 A>C), RS1000140152 (6:147546430 T>C,G)

Disease associations

OMIM: gene MIM:620517 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

9 associations (top):

Study	Trait	p-value
GCST001762_698	Obesity-related traits	8.000000e-06
GCST003831_41	Asthma	9.000000e-06
GCST003988_12	Hypothyroidism	1.000000e-14
GCST005588_30	Idiopathic dilated cardiomyopathy	9.000000e-06
GCST006873_1	Subiculum volume (corrected for total hippocampal volume)	6.000000e-09
GCST006952_27	Feeling tense	5.000000e-09
GCST007576_196	Chronotype	7.000000e-09
GCST008226_2	Renal cell carcinoma	2.000000e-08
GCST010653_28	Thyroid stimulating hormone levels	1.000000e-17

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0005116	urinary metabolite measurement
EFO:0009094	idiopathic dilated cardiomyopathy
EFO:0009596	feeling tense measurement
EFO:0008328	chronotype measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Aflatoxin B1	affects expression, decreases methylation, increases expression	4
Valproic Acid	affects expression, increases expression	3
Vorinostat	affects cotreatment, increases expression	2
Benzo(a)pyrene	increases expression, increases methylation	2
Diethylhexyl Phthalate	decreases expression, increases abundance, increases methylation	2
Estradiol	increases expression, affects cotreatment, decreases expression	2
Nickel	decreases expression	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Tobacco Smoke Pollution	decreases expression, increases expression	2
geldanamycin	increases expression	1
mono-(2-ethylhexyl)phthalate	increases abundance, increases methylation	1
manganese chloride	increases abundance, increases expression	1
benzo(e)pyrene	increases methylation	1
monomethylarsonous acid	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
licochalcone B	decreases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Temozolomide	increases expression	1
Decitabine	decreases expression, affects reaction	1
Air Pollutants	decreases expression, increases abundance	1
Vehicle Emissions	decreases expression, increases abundance	1
Lipopolysaccharides	affects cotreatment, decreases expression	1
Manganese	increases abundance, increases expression	1
Methapyrilene	increases methylation	1
Rotenone	increases expression	1
Silicon Dioxide	increases expression	1
Smoke	increases expression	1
Tretinoin	increases expression	1
Triclosan	increases expression	1

Clinical trials (associated diseases)

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