ST7

Summary

ST7 (suppression of tumorigenicity 7, HGNC:11351) is a protein-coding gene on chromosome 7q31.2, encoding Suppressor of tumorigenicity 7 protein (Q9NRC1). May act as a tumor suppressor.

The gene for this product maps to a region on chromosome 7 identified as an autism-susceptibility locus. Mutation screening of the entire coding region in autistic individuals failed to identify phenotype-specific variants, suggesting that coding mutations for this gene are unlikely to be involved in the etiology of autism. The function of this gene product has not been determined. Transcript variants encoding different isoforms of this protein have been described.

Source: NCBI Gene 7982 — RefSeq curated summary.

At a glance

• Gene–disease (curated): genetic developmental and epileptic encephalopathy (Limited, GenCC)
• GWAS associations: 8
• Clinical variants (ClinVar): 65 total — 1 likely-pathogenic
• Regional missense constraint (gnomAD): 1 of 4 regions constrained (≈10% of expected missense variation)
• GTEx eGene: eQTL in 11 tissues, sQTL in 4 (q < 0.05)
• Constraint (gnomAD): pLI 0.92 (loss-of-function intolerant), LOEUF 0.52 (moderately constrained)
• MANE Select transcript: NM_001369598
• Notable: 65 clinical variants but no curated precision-oncology (CIViC) evidence yet

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11351
Approved symbol	ST7
Name	suppression of tumorigenicity 7
Location	7q31.2
Locus type	gene with protein product
Status	Approved
Aliases	TSG7, SEN4, ETS7q, HELG, RAY1, FAM4A
Ensembl gene	ENSG00000004866
Ensembl biotype	protein_coding
OMIM	600833
Entrez	7982

Gene structure

Transcript identifiers

Ensembl transcripts: 49 — 34 protein_coding, 7 nonsense_mediated_decay, 7 protein_coding_CDS_not_defined, 1 retained_intron

MANE Select: ENST00000323984

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 5, TSL 2: 2, TSL 3: 1, TSL 4: 4, TSL 5: 16

ENST00000323984, ENST00000265437, ENST00000393443, ENST00000393444, ENST00000393446, ENST00000393447, ENST00000393449, ENST00000393451, ENST00000417919, ENST00000420755, ENST00000422922, ENST00000432298, ENST00000434836, ENST00000438863, ENST00000443979, ENST00000446490, ENST00000449366, ENST00000462544, ENST00000464020, ENST00000465133, ENST00000465641, ENST00000467538, ENST00000477742, ENST00000485394, ENST00000487459, ENST00000489293, ENST00000490039, ENST00000543837, ENST00000903532, ENST00000903533, ENST00000903534, ENST00000923796, ENST00000923797, ENST00000923798, ENST00000946966, ENST00000946967, ENST00001000364, ENST00001000368, ENST00001000369, ENST00001035063, ENST00001035065, ENST00001060380, ENST00001092555, ENST00001109257, ENST00001109258, ENST00001112887, ENST00001112888, ENST00001112889, ENST00001136627

RefSeq mRNA: 11 — MANE Select: NM_001369598 NM_001369598, NM_001369599, NM_001369600, NM_001369601, NM_001369602, NM_001369603, NM_001369604, NM_001369606, NM_001369607, NM_018412, NM_021908

CCDS: CCDS5769, CCDS5770, CCDS94181, CCDS94182, CCDS94183, CCDS94184, CCDS94185, CCDS94186

Canonical transcript exons

ENST00000323984 — 16 exons

Exon	Start	End
ENSE00003475093	117190834	117190936
ENSE00003496919	117219084	117219176
ENSE00003536623	117221923	117222062
ENSE00003539042	117138435	117138532
ENSE00003577586	117134124	117134192
ENSE00003586100	117130491	117130606
ENSE00003619513	117136081	117136235
ENSE00003621647	117189321	117189393
ENSE00003633228	117099762	117099844
ENSE00003641370	117170862	117170976
ENSE00003678758	117209787	117209937
ENSE00003683670	117131885	117131960
ENSE00003684887	117119561	117119720
ENSE00003787786	117129793	117129847
ENSE00003907709	116953501	116953691
ENSE00003909160	117229762	117230176

Expression profiles

Bgee: expression breadth ubiquitous, 281 present calls, max score 95.25.

FANTOM5 (CAGE): breadth broad, TPM avg 5.6107 / max 272.2260, expressed in 735 samples.

Highest expression (Bgee): cortical plate, ventricular zone, ganglionic eminence, cerebellar hemisphere, cerebellar cortex.

Genetic regulation across tissues (GTEx eQTL / sQTL)

ST7 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 11 tissues and its splicing (sQTL) in 4 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

15 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Brain Cerebellar Hemisphere	eqtl	2.6e-23	-0.66	7:117083842:G:A
Brain Cerebellum	eqtl	1.3e-20	-0.73	7:117083842:G:A
Testis	eqtl	3.5e-19	-0.68	7:117177738:C:G
Testis	sqtl	7.0e-19	+0.84	7:117165458:C:T
Skin Sun Exposed Lower leg	sqtl	1.7e-04	+0.61	7:117162258:G:A
Artery Tibial	eqtl	2.2e-03	-0.09	7:116941511:G:A
Adipose Subcutaneous	sqtl	6.6e-03	+0.54	7:117166655:T:C
Muscle Skeletal	eqtl	2.0e-02	+0.50	7:116573079:G:A
Artery Aorta	eqtl	2.0e-02	+0.32	7:116109902:A:G
Cells Cultured fibroblasts	eqtl	2.7e-02	+0.17	7:117159533:T:C
Spleen	eqtl	2.7e-02	+0.30	7:117166655:T:C
Skin Sun Exposed Lower leg	eqtl	4.1e-02	-0.12	7:116475620:GT:G
Pancreas	eqtl	4.2e-02	+0.30	7:116687978:C:T
Skin Not Sun Exposed Suprapubic	sqtl	4.4e-02	+0.51	7:117163774:G:A
Brain Hypothalamus	eqtl	5.0e-02	-0.21	7:117195680:C:T

FANTOM5 promoters

showing 10 of 14 alternative TSS:

Promoter ID	TPM avg	Samples expressed
80693	11.1244	1773
80691	6.0297	1686
80703	5.6107	735
80700	2.8840	365
80694	0.9908	663
80704	0.5586	259
80692	0.4734	261
80699	0.2838	138
204665	0.2338	84
80709	0.2148	39

Top tissues by expression

showing 100 of 292 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
cortical plate	UBERON:0005343	95.25	gold quality
ventricular zone	UBERON:0003053	92.74	gold quality
ganglionic eminence	UBERON:0004023	92.44	gold quality
cerebellar hemisphere	UBERON:0002245	91.87	gold quality
cerebellar cortex	UBERON:0002129	91.73	gold quality
body of pancreas	UBERON:0001150	91.69	gold quality
popliteal artery	UBERON:0002250	91.66	gold quality
tibial artery	UBERON:0007610	91.63	gold quality
right hemisphere of cerebellum	UBERON:0014890	91.54	gold quality
right coronary artery	UBERON:0001625	90.94	gold quality
aorta	UBERON:0000947	90.89	gold quality
right lung	UBERON:0002167	90.84	gold quality
cerebellum	UBERON:0002037	90.66	gold quality
islet of Langerhans	UBERON:0000006	90.63	gold quality
pancreas	UBERON:0001264	90.33	gold quality
ascending aorta	UBERON:0001496	90.25	gold quality
thoracic aorta	UBERON:0001515	90.17	gold quality
right atrium auricular region	UBERON:0006631	90.09	gold quality
right lobe of liver	UBERON:0001114	90.08	gold quality
left lobe of thyroid gland	UBERON:0001120	89.94	gold quality
left coronary artery	UBERON:0001626	89.74	gold quality
upper lobe of left lung	UBERON:0008952	89.61	gold quality
right adrenal gland	UBERON:0001233	89.58	gold quality
right adrenal gland cortex	UBERON:0035827	89.51	gold quality
right lobe of thyroid gland	UBERON:0001119	89.50	gold quality
left adrenal gland	UBERON:0001234	89.45	gold quality
middle temporal gyrus	UBERON:0002771	89.44	gold quality
thyroid gland	UBERON:0002046	89.39	gold quality
left adrenal gland cortex	UBERON:0035825	89.30	gold quality
pituitary gland	UBERON:0000007	89.29	gold quality
descending thoracic aorta	UBERON:0002345	89.23	gold quality
upper lobe of lung	UBERON:0008948	89.23	gold quality
adenohypophysis	UBERON:0002196	89.18	gold quality
apex of heart	UBERON:0002098	88.99	gold quality
coronary artery	UBERON:0001621	88.92	gold quality
parotid gland	UBERON:0001831	88.89	gold quality
cardiac atrium	UBERON:0002081	88.87	gold quality
heart left ventricle	UBERON:0002084	88.53	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	88.33	gold quality
adrenal gland	UBERON:0002369	88.30	gold quality
liver	UBERON:0002107	88.15	gold quality
heart	UBERON:0000948	88.10	gold quality
cardiac ventricle	UBERON:0002082	88.06	gold quality
adrenal cortex	UBERON:0001235	87.88	gold quality
hindlimb stylopod muscle	UBERON:0004252	87.32	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	87.01	gold quality
right uterine tube	UBERON:0001302	86.62	gold quality
body of stomach	UBERON:0001161	86.61	gold quality
stromal cell of endometrium	CL:0002255	86.44	gold quality
right frontal lobe	UBERON:0002810	86.38	gold quality
Brodmann (1909) area 23	UBERON:0013554	86.22	gold quality
adrenal tissue	UBERON:0018303	86.09	gold quality
lung	UBERON:0002048	86.01	gold quality
stomach	UBERON:0000945	85.93	gold quality
left ovary	UBERON:0002119	85.84	gold quality
left uterine tube	UBERON:0001303	85.76	gold quality
Brodmann (1909) area 9	UBERON:0013540	85.75	gold quality
metanephros cortex	UBERON:0010533	85.54	gold quality
cingulate cortex	UBERON:0003027	85.42	gold quality
endocervix	UBERON:0000458	85.38	gold quality
right ovary	UBERON:0002118	85.38	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	85.37	gold quality
anterior cingulate cortex	UBERON:0009835	85.31	gold quality
muscle layer of sigmoid colon	UBERON:0035805	85.15	gold quality
body of uterus	UBERON:0009853	84.97	gold quality
gall bladder	UBERON:0002110	84.95	gold quality
prefrontal cortex	UBERON:0000451	84.92	gold quality
mucosa of stomach	UBERON:0001199	84.85	gold quality
ectocervix	UBERON:0012249	84.82	gold quality
omental fat pad	UBERON:0010414	84.69	gold quality
peritoneum	UBERON:0002358	84.63	gold quality
adult mammalian kidney	UBERON:0000082	84.62	gold quality
rectum	UBERON:0001052	84.49	gold quality
muscle of leg	UBERON:0001383	84.47	gold quality
saliva-secreting gland	UBERON:0001044	84.44	gold quality
lower esophagus muscularis layer	UBERON:0035833	84.39	gold quality
lower esophagus	UBERON:0013473	84.36	gold quality
gastrocnemius	UBERON:0001388	84.27	gold quality
paraflocculus	UBERON:0005351	84.20	gold quality
neocortex	UBERON:0001950	84.14	gold quality
calcaneal tendon	UBERON:0003701	84.12	gold quality
seminal vesicle	UBERON:0000998	83.97	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	83.96	gold quality
minor salivary gland	UBERON:0001830	83.95	gold quality
caudate nucleus	UBERON:0001873	83.82	gold quality
adipose tissue of abdominal region	UBERON:0007808	83.75	gold quality
amygdala	UBERON:0001876	83.74	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	83.68	gold quality
primary visual cortex	UBERON:0002436	83.56	gold quality
frontal cortex	UBERON:0001870	83.44	gold quality
nephron tubule	UBERON:0001231	83.41	gold quality
ovary	UBERON:0000992	83.36	gold quality
Brodmann (1909) area 10	UBERON:0013541	83.28	gold quality
skin of leg	UBERON:0001511	83.26	gold quality
nucleus accumbens	UBERON:0001882	83.19	gold quality
smooth muscle tissue	UBERON:0001135	83.18	gold quality
subcutaneous adipose tissue	UBERON:0002190	83.15	gold quality
brain	UBERON:0000955	83.06	gold quality
cortex of kidney	UBERON:0001225	83.02	gold quality
central nervous system	UBERON:0001017	82.92	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-GEOD-93593	yes	10.88
E-ANND-3	no	0.00

HPA expression

RNA tissue specificity: Low tissue specificity

showing 60 of 79 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Cerebellum	tissue	73.8	low
Postcentral gyrus	tissue	44.1
Liver	tissue	38.6	not detected
Epididymis	tissue	33.8	not detected
Hippocampus	tissue	31.8	not detected
Nucleus accumbens	tissue	31.4
Pancreas	tissue	31.0	medium
Locus coeruleus	tissue	30.8
Kidney	tissue	27.4	medium
Thyroid gland	tissue	26.6	medium
Lung	tissue	24.6	low
Pituitary gland	tissue	23.3
Salivary gland	tissue	20.4	low
Choroid plexus	tissue	20.2
Olfactory bulb	tissue	20.1
Seminal vesicle	tissue	19.9	not detected
Placenta	tissue	19.6	medium
Cerebral cortex	tissue	19.3	low
Retrosplenial and cingulate cortex	tissue	19.3
Cervix	tissue	18.8	low
Occipital cortex	tissue	18.1
Retrosplenial cortex	tissue	18.0
Parathyroid gland	tissue	17.9	low
Motor cortex	tissue	17.9
Hippocampal formation	tissue	17.9
Entorhinal cortex	tissue	17.9
Prefrontal cortex	tissue	17.7
Adrenal gland	tissue	17.7	medium
Fallopian tube	tissue	17.5	medium
Somatosensory cortex	tissue	17.3
Insular cortex	tissue	17.3
Hypothalamus	tissue	17.2
Bone marrow	tissue	16.8	not detected
Basal ganglia	tissue	16.7	low
Septum	tissue	16.0
Temporal cortex	tissue	15.8
Pons	tissue	15.2
Ventral forebrain	tissue	15.2
Heart muscle	tissue	15.1	medium
Stomach 1	tissue	15.0	low
Amygdala	tissue	15.0
Putamen	tissue	14.7
Breast	tissue	14.2	medium
Midbrain	tissue	14.2
Periaqueductal gray	tissue	14.2
Superior colliculi	tissue	14.0
Ovary	tissue	13.9	not detected
Endometrium 1	tissue	13.6	medium
Thalamus	tissue	13.6
Prostate	tissue	12.9	low
Medulla oblongata	tissue	12.7
Substantia nigra	tissue	12.5
Adipose tissue	tissue	12.2	low
Smooth muscle	tissue	11.8	low
Urinary bladder	tissue	11.8	low
Retina	tissue	11.7
Rectum	tissue	11.7	medium
Skeletal muscle	tissue	11.7	medium
Gallbladder	tissue	11.6	medium
Duodenum	tissue	11.4	medium

Brain sub-regions (HPA Brain Atlas): detected in 292; highest nTPM — Flocculonodular lobe (101.7), Vermis (100.1), Cerebellar cortex (99.4), Arcuate nucleus (44.5), Ventromedial nucleus (43.9).

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): SMARCA1

miRNA regulators (miRDB)

Targeting ST7 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 68 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-450A-1-3P	100.00	69.33	1837
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-499A-5P	99.98	70.79	1323
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-101-3P	99.94	75.03	2230
HSA-MIR-144-3P	99.94	73.98	2698
HSA-MIR-1305	99.91	71.43	3443
HSA-MIR-4493	99.90	66.48	977
HSA-MIR-95-5P	99.89	72.17	3973
HSA-MIR-605-3P	99.88	69.22	1833
HSA-MIR-6857-5P	99.87	65.32	985
HSA-MIR-4779	99.86	66.50	1583
HSA-MIR-4447	99.85	67.81	2900
HSA-MIR-369-3P	99.85	70.52	2264
HSA-MIR-765	99.84	68.24	2442
HSA-MIR-6739-5P	99.80	67.87	2806
HSA-MIR-92A-2-5P	99.75	67.01	2164
HSA-MIR-11181-3P	99.75	66.38	2205
HSA-MIR-6733-5P	99.74	67.94	2759
HSA-MIR-1255A	99.74	68.09	744
HSA-MIR-1255B-5P	99.74	68.16	741
HSA-MIR-518A-5P	99.70	69.01	2209
HSA-MIR-527	99.70	69.01	2209
HSA-MIR-4729	99.69	72.18	4233
HSA-MIR-3660	99.68	67.33	1149
HSA-MIR-4526	99.68	67.07	1136
HSA-MIR-580-3P	99.67	69.23	1841
HSA-MIR-4756-3P	99.62	66.30	1319
HSA-MIR-6126	99.62	68.09	996

Functional genomics

gnomAD constraint: pLI 0.922, LOEUF 0.52, missense Z 3.7 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD)

ENST00000323984 splits into 4 regions with different missense tolerance; 1 is missense-constrained (≈10% of the expected missense variation). Missense variants in a constrained region (low observed/expected) are more likely to be pathogenic. gnomAD

Region (GRCh38)	Missense obs / exp	o/e	Constrained
7:116,953,541–116,953,691	71 / 61.5	1.16	no
7:117,099,762–117,119,642	23 / 67.7	0.34	yes (p 5.5e-08)
7:117,119,643–117,119,718	36 / 29.7	1.21	no
7:117,119,719–117,229,854	288 / 537.1	0.54	no

Literature-anchored findings (GeneRIF, showing 9)

• Mutational analysis of ST7 in a wide range of cell lines and primary epithelial cancer failed to detect mutations at this locus, with the exception of 1 missense change in a breast cancer cell line. (PMID:12107844)
• The RAY1/ST7 tumor-suppressor locus on chromosome 7q31 represents a complex multi-transcript system (PMID:12213198)
• The ST7 gene is not a primary target of inactivation in most human cancers with loss of heterozygosity at 7q31.1-q31.2. (PMID:12231539)
• These data suggest that LOH at 7q31-q35 is involved in the origin or progression of at least a subset of esophageal carcinomas, but that ST7 is not the target gene of this somatic event. (PMID:12545169)
• somatic mutations of ST7 do not commonly contribute to the molecular pathogenesis of human malignant myeloid tumors (PMID:14534688)
• ST7 gene may not be the target gene of inactivation at 7q31 site in gastric carcinoma. (PMID:14669308)
• ST7 mediates tumor suppression through the regulation of the genes involved in maintaining the cellular structure of the cell and involved in oncogenic pathways (PMID:20238225)
• The tumor suppressor ST7 is a key gene silenced by PRMT5. (PMID:24453002)
• Inflammation-dependent overexpression of c-Myc enhances CRL4(DCAF4) E3 ligase activity and promotes ubiquitination of ST7 in colitis-associated cancer. (PMID:30945288)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
mus_musculus	St7	ENSMUSG00000029534
rattus_norvegicus	St7	ENSRNOG00000056243
drosophila_melanogaster	CG3634	FBGN0037026
caenorhabditis_elegans		WBGENE00008686

Paralogs (1): ST7L (ENSG00000007341)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:1927450) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 5 distinct phenotype terms.

Mouse phenotype (MP)	Records
abnormal coat/ hair morphology	1
hyperactivity	1
abnormal vocalization	1
abnormal coat/hair pigmentation	1
decreased mean corpuscular volume	1

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Felis catus	A0M8T1	100.0%	Diamond
Bos taurus	A4D7R9	100.0%	Diamond
Aotus nancymaae	Q07DV5	100.0%	Diamond
Muntiacus reevesi	Q07DW9	100.0%	Diamond
Colobus guereza	Q07DY8	100.0%	Diamond
Saimiri boliviensis boliviensis	Q09YH4	100.0%	Diamond
Ovis aries	Q09YI5	100.0%	Diamond
Muntiacus muntjak	Q09YJ7	100.0%	Diamond
Ateles geoffroyi	Q09YK8	100.0%	Diamond
Chlorocebus aethiops	Q2IBA8	100.0%	Diamond
Gorilla gorilla gorilla	Q2IBE8	100.0%	Diamond
Equus caballus	Q2QLA6	100.0%	Diamond
Plecturocebus moloch	Q2QLB7	100.0%	Diamond
Sus scrofa	Q2QLD7	100.0%	Diamond
Pan troglodytes	Q2QLE8	100.0%	Diamond
Papio anubis	A0M8S0	99.8%	Diamond
Nomascus leucogenys	Q07DX8	99.8%	Diamond
Pongo abelii	Q2IBE0	99.8%	Diamond
Callithrix jacchus	Q2QLG2	99.8%	Diamond
Loxodonta africana	Q108U3	99.7%	Diamond
Macaca fascicularis	Q2PG42	99.6%	Diamond
Rhinolophus ferrumequinum	Q00PJ0	99.5%	Diamond
Oryctolagus cuniculus	Q09YN2	99.5%	Diamond
Dasypus novemcinctus	Q07E45	99.1%	Diamond
Microcebus murinus	Q2QL86	99.1%	Diamond
Cavia porcellus	Q07E08	99.0%	Diamond
Drosophila pseudoobscura pseudoobscura	Q2M146	97.2%	Diamond
Gallus gallus	A0M8U1	94.7%	Diamond
Danio rerio	Q1RLU8	94.7%	Diamond
Caenorhabditis briggsae	A8X0L4	88.2%	Diamond
Nematostella vectensis	A7S641	71.0%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
WNT2	protein-coding	7472
ST7-OT3	ncRNA	93655
ST7-OT4	ncRNA	338069
CAPZA2	protein-coding	830
ST7-AS1	ncRNA	93653
ST7-AS2	ncRNA	93654
MIR6132	ncRNA	102466616
MET	protein-coding	4233

Protein

Protein identifiers

Suppressor of tumorigenicity 7 protein — Q9NRC1 (reviewed: Q9NRC1)

Alternative names: Protein FAM4A1, Protein HELG

All UniProt accessions (19): Q9NRC1, B7Z4L1, B7Z4U3, C9J2Z1, C9JRQ0, C9JRW1, C9JU30, C9JWK8, C9JX79, C9JZV9, E7EMS3, E7ENZ9, E7EPD9, E7EPW5, E9PCV1, E9PF01, G3XAH9, H7BXS2, X5DRA0

UniProt curated annotations — full annotation on UniProt →

Function. May act as a tumor suppressor.

Subcellular location. Membrane.

Tissue specificity. Ubiquitously expressed, with highest levels in heart, liver and pancreas.

Similarity. Belongs to the ST7 family.

Isoforms (7)

UniProt ID	Names	Canonical?
Q9NRC1-1	1	yes
Q9NRC1-2	2
Q9NRC1-3	3
Q9NRC1-4	4
Q9NRC1-5	5
Q9NRC1-6	6
Q9NRC1-7	7

RefSeq proteins (11): NP_001356527, NP_001356528, NP_001356529, NP_001356530, NP_001356531, NP_001356532, NP_001356533, NP_001356535, NP_001356536, NP_060882, NP_068708 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR007311	ST7	Family

Pfam: PF04184

UniProt features (18 total): splice variant 10, transmembrane region 3, sequence variant 2, chain 1, modified residue 1, glycosylation site 1

Structure

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9NRC1-F1	80.60	0.47

Human Protein Atlas

Protein class: Predicted membrane proteins, Predicted intracellular proteins

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): nucleoplasm; cytosol

Antibody reliability (HPA): IH approved · IF supported

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)

Type	Positions
Phosphoserine	386

Glycosylation sites (1)

Type	Positions
N-linked (glcnac…) asparagine	47

Function

Pathways and Gene Ontology

Reactome pathways

0 curated (TAS) of 0; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

MSigDB gene sets: 186 (showing top): FXR_IR1_Q6, MIDORIKAWA_AMPLIFIED_IN_LIVER_CANCER, PAL_PRMT5_TARGETS_UP, ENK_UV_RESPONSE_KERATINOCYTE_UP, BROWNE_HCMV_INFECTION_16HR_UP, BROWNE_HCMV_INFECTION_24HR_UP, AAAGGGA_MIR204_MIR211, BROWN_MYELOID_CELL_DEVELOPMENT_DN, CDPCR3HD_01, AP2_Q6_01, NELSON_RESPONSE_TO_ANDROGEN_DN, RIZKI_TUMOR_INVASIVENESS_3D_UP, LIU_SOX4_TARGETS_DN, ASGHARZADEH_NEUROBLASTOMA_POOR_SURVIVAL_DN, chr7q31

GO Biological Process (2): extracellular matrix organization (GO:0030198), regulation of cell differentiation (GO:0045595)

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

GO Cellular Component (2): nucleoplasm (GO:0005654), membrane (GO:0016020)

GO top-level categories

8 GO namespaces:

Category	Terms
cellular anatomical structure	2
extracellular structure organization	1
external encapsulating structure organization	1
cell differentiation	1
regulation of developmental process	1
regulation of cellular process	1
binding	1
nuclear lumen	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 1 of 5 annotations. The rest are phylogenetic / computational / electronic (IEA).

1 experimentally-supported GO terms:

GO term	NS	Evidence
nucleoplasm	CC	direct assay

Protein interactions and networks

STRING

showing 15 of 764 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ST7	FOXP2	O15409	608
ST7	WNT2	P09544	561
ST7	TSEN2	Q8NCE0	539
ST7	MET	P08581	478
ST7	DCAF4	Q8WV16	437
ST7	IMMP2L	Q96T52	429
ST7	PDCD7	Q8N8D1	422
ST7	DVL1	O14640	420
ST7	CUL4A	Q13619	397
ST7	TSEN34	Q9BSV6	380
ST7	FXYD2	P54710	364
ST7	TPRG1L	Q5T0D9	323
ST7	SETX	Q7Z333	315
ST7	DENND2B	P78523	300
ST7	TUSC1	Q2TAM9	281

IntAct

Human interaction partners of ST7 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

3 partners by confidence:

Partner	Interaction type	MIscore	Records
DCAF4	physical association	0.500	2
NFKBIA	physical association	0.370	1
A2ML1	association	0.350	1

BioGRID (431 interactions; top human partners by supporting records): CHRNA9 (Affinity Capture-MS; 3 records), CUL4A (Affinity Capture-Western; 3 records), CUL4B (Affinity Capture-Western; 3 records), DCAF4 (Affinity Capture-Western; 3 records), HLA-DQA1 (Affinity Capture-MS; 3 records), NMRK2 (Affinity Capture-Western; 3 records), B4GAT1 (Affinity Capture-MS; 2 records), C3AR1 (Affinity Capture-MS; 2 records), CD244 (Affinity Capture-MS; 2 records), CDH5 (Affinity Capture-MS; 2 records), CHRND (Affinity Capture-MS; 2 records), CKAP4 (Proximity Label-MS; 2 records), DNAJC1 (Proximity Label-MS; 2 records), DNAJC16 (Proximity Label-MS; 2 records), EMD (Proximity Label-MS; 2 records)

SIGNOR signaling

3 signaling interactions:

A	Effect	B	Mechanism
DCAF4	“down-regulates quantity by destabilization”	ST7	binding
Cullin4-RBX1-DDB1	“down-regulates quantity by destabilization”	ST7	polyubiquitination
SMARCA1	“down-regulates quantity by repression”	ST7	“transcriptional regulation”

Disease & clinical

Genetic variants

Variant evidence for ST7: 65 ClinVar records (1 pathogenic / likely pathogenic); 8 GWAS associations. Per-variant detail is on Sugi Variant.

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	1
Uncertain significance	41
Likely benign	7
Benign	3

Top pathogenic / likely-pathogenic (1)

Showing all 1 pathogenic / likely-pathogenic ClinVar records, ranked by ClinVar review status (expert panel → multiple submitters → single submitter), then by number of submitting labs.

Variant ID	HGVS	Classification	Review	Submitters
183291	NM_001369598.1(ST7):c.489T>G (p.Tyr163Ter)	Likely pathogenic	no assertion criteria provided	1

Per-variant reference — Sugi Variant

Explore ST7’s pathogenic and likely-pathogenic variants individually — each with its ClinVar classification and conditions, applied ACMG criteria (ClinGen expert panel, where curated), the calibrated in-silico predictors (AlphaMissense, REVEL, SaProt, conservation), gnomAD frequency, and the predictor-disagreement QC signal — on Sugi Variant.

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 39 predictions of 2,316):

Position(s)	Effect	Δscore	Sites
7:116953692	donor_loss	1.0000	2
7:117099845–117099846	donor_loss	1.0000	5
7:117119559–117119560	acceptor_loss	1.0000	4
7:117119721–117119722	donor_loss	1.0000	5
7:117130489–117130490	acceptor_loss	1.0000	4
7:117138509	donor_gain	1.0000
7:117170977–117170978	donor_loss	1.0000	5
7:117189319–117189320	acceptor_loss	1.0000	6
7:117189394–117189395	donor_loss	1.0000	5
7:116953693	donor_loss	0.9900	2

AlphaMissense

2,542 missense substitutions predicted likely pathogenic (of 3,770 scored), across 477 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
M165	9	0.991	1.000
M190	9	0.982	1.000
M304	9	0.914	0.996
M540	9	0.880	0.990
M319	9	0.873	0.995
D164	8	1.000	1.000
N166	8	0.999	1.000
D171	8	0.999	1.000
H172	8	0.999	1.000
D438	8	0.999	1.000
F176	8	0.998	1.000
H432	8	0.998	0.999
F92	8	0.997	1.000
D359	8	0.997	1.000
H407	8	0.997	1.000
F483	8	0.997	1.000
F62	8	0.996	1.000
D291	8	0.996	1.000
H415	8	0.996	1.000
F470	8	0.996	1.000

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

3 prognostic cancer types:

Cancer	Prognostic	p-value
Kidney Renal Clear Cell Carcinoma (TCGA)	favorable	2.23e-06
Kidney Renal Clear Cell Carcinoma (TCGA)	favorable	5.59e-05
Glioblastoma Multiforme (validation)	favorable	0.000111

Disease associations

OMIM: gene MIM:600833 | disease phenotypes:

GenCC curated gene-disease

1 curated gene-disease records:

Disease	Classification	Inheritance	Records
genetic developmental and epileptic encephalopathy	Limited	Autosomal recessive

Mondo (1): genetic developmental and epileptic encephalopathy (MONDO:0100062)

GWAS associations

8 associations:

Study	Trait	p-value
GCST010796_3033	Electrocardiogram morphology (amplitude at temporal datapoints)	6e-10
GCST010796_3031	Electrocardiogram morphology (amplitude at temporal datapoints)	8e-10
GCST005956_33	Waist-to-hip ratio adjusted for BMI	5e-9
GCST010796_3032	Electrocardiogram morphology (amplitude at temporal datapoints)	2e-8
GCST007998_2	Intraocular pressure	1e-7
GCST005962_14	Waist-to-hip ratio adjusted for BMI x sex x age interaction (4df test)	3e-7
GCST001629_2	Response to platinum-based chemotherapy in non-small-cell lung cancer	4e-7
GCST005439_5	Response to alcohol consumption (flushing response)	3e-6

EFO canonical traits (from GWAS)

5 canonical traits:

EFO ID	Trait name
EFO:0007788	BMI-adjusted waist-hip ratio
EFO:0008007	age at assessment
EFO:0008343	sex interaction measurement
EFO:0004695	intraocular pressure measurement
EFO:0004327	electrocardiography

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (CPIC guideline: no)

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	decreases expression	3
Valproic Acid	decreases expression, increases expression, affects expression	3
methylselenic acid	decreases expression, affects expression	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Testosterone	affects cotreatment, decreases expression	2
Aflatoxin B1	decreases expression, decreases methylation	2
aristolochic acid I	decreases expression	1
testosterone enanthate	affects expression	1
triphenyl phosphate	affects expression	1
alpha-pinene	affects cotreatment, increases expression, increases abundance	1
bisphenol A	decreases methylation	1
trichostatin A	affects expression	1
tris(2-butoxyethyl) phosphate	affects expression	1
beta-lapachone	decreases expression, increases expression	1
methacrylaldehyde	increases abundance, affects cotreatment, increases expression	1
lei gong teng	increases expression	1
beta-methylcholine	affects expression	1
epigallocatechin gallate	increases expression	1
glycidamide	decreases expression	1
CGP 52608	affects binding, increases reaction	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	increases expression, affects cotreatment	1
dorsomorphin	affects cotreatment, increases expression	1
picoxystrobin	decreases expression	1
Acetaminophen	decreases expression	1
Acrolein	affects cotreatment, increases expression, increases abundance	1
Air Pollutants	affects cotreatment, increases abundance, increases expression	1
Calcitriol	decreases expression, affects cotreatment	1
Cisplatin	decreases expression	1
Doxorubicin	decreases expression	1
Estradiol	decreases expression, affects cotreatment	1

Clinical trials (associated diseases)

Via MONDO — disease-level, not drug-specific.

12 trials:

NCT	Phase	Status	Title
NCT06719141	Phase 3	ACTIVE_NOT_RECRUITING	A Study to Investigate LP352 in Children and Adults With Developmental and Epileptic Encephalopathies (DEE)
NCT06908226	Phase 3	ENROLLING_BY_INVITATION	A Study to Investigate LP352 in Children and Adults With Developmental and Epileptic Encephalopathy (DEE)
NCT07723976	Phase 3	NOT_YET_RECRUITING	A Study to Evaluate the Safety and Efficacy of CBD-OS in Participants With DEE
NCT05626634	Phase 2	COMPLETED	Open-label, Long-term Safety Study of LP352 in Subjects With Developmental and Epileptic Encephalopathy
NCT06700811	Phase 1	RECRUITING	Ketogenic Diet for Prevention of Epileptic Spasms in Infantile Onset Genetic Epilepsies
NCT05364021	Phase 1/2	COMPLETED	Study to Investigate LP352 in Subjects With Developmental and Epileptic Encephalopathies
NCT06983158	Phase 1/2	TERMINATED	A Clinical Trial of CAP-002 Gene Therapy in Pediatric Patients With Syntaxin-Binding Protein 1 (STXBP1) Encephalopathy
NCT04937062	Early Phase 1	ACTIVE_NOT_RECRUITING	Phenylbutyrate for Monogenetic Developmental and Epileptic Encephalopathy
NCT06149663	Not specified	AVAILABLE	Intermediate-Size Expanded Access Protocol (EAP) for LP352
NCT06380192	Not specified	RECRUITING	Developmental and Epileptic Encephalopathy of Genetic Etiology: Natural History Through Reuse of Clinical Data
NCT07396883	Not specified	NOT_YET_RECRUITING	Developmental and Epileptic Encephalopathies Diagnosed Via Long-read Genome Sequencing
NCT07585643	Not specified	NOT_YET_RECRUITING	IBIS - Investigating Reliability of BIS and SEDLINE Monitoring in Children With Developmental and Epileptic Encephalopathies (DEE).