TSPAN1

Summary

TSPAN1 (tetraspanin 1, HGNC:20657) is a protein-coding gene on chromosome 1p34.1, encoding Tetraspanin-1 (O60635). Structural component of specialized membrane microdomains known as tetraspanin-enriched microdomains (TERMs), which act as platforms for receptor clustering and signaling.

The protein encoded by this gene is a member of the transmembrane 4 superfamily, also known as the tetraspanin family. Most of these members are cell-surface proteins that are characterized by the presence of four hydrophobic domains. The proteins mediate signal transduction events that play a role in the regulation of cell development, activation, growth and motility.

Source: NCBI Gene 10103 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 511 total — 22 pathogenic, 28 likely-pathogenic
• Phenotypes (HPO): 1
• MANE Select transcript: NM_005727

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:20657
Approved symbol	TSPAN1
Name	tetraspanin 1
Location	1p34.1
Locus type	gene with protein product
Status	Approved
Aliases	TSPAN-1, NET-1
Ensembl gene	ENSG00000117472
Ensembl biotype	protein_coding
OMIM	613170
Entrez	10103

Gene structure

Transcript identifiers

Ensembl transcripts: 27 — 19 protein_coding, 8 protein_coding_CDS_not_defined

ENST00000372003, ENST00000464786, ENST00000469330, ENST00000470318, ENST00000472170, ENST00000475163, ENST00000482143, ENST00000482928, ENST00000498443, ENST00000893420, ENST00000893421, ENST00000893422, ENST00000893423, ENST00000893424, ENST00000893425, ENST00000893426, ENST00000893427, ENST00000893428, ENST00000893429, ENST00000893430, ENST00000893431, ENST00000972185, ENST00000972186, ENST00000972187, ENST00000972188, ENST00000972189, ENST00000972190

RefSeq mRNA: 1 — MANE Select: NM_005727 NM_005727

CCDS: CCDS530

Canonical transcript exons

ENST00000372003 — 9 exons

Exon	Start	End
ENSE00000902595	46185486	46185962
ENSE00001456673	46180526	46180658
ENSE00001456674	46175087	46175409
ENSE00003489855	46185225	46185308
ENSE00003543902	46184191	46184397
ENSE00003549014	46184594	46184668
ENSE00003607443	46184785	46184883
ENSE00003615129	46181100	46181164
ENSE00003686605	46184960	46185115

Expression profiles

Bgee: expression breadth ubiquitous, 206 present calls, max score 99.85.

FANTOM5 (CAGE): breadth broad, TPM avg 11.8997 / max 928.5774, expressed in 432 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
2722	11.4428	366
2720	0.1635	5
2719	0.1586	80
2724	0.0880	45
2725	0.0382	15
2721	0.0085	4

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
bronchial epithelial cell	CL:0002328	99.85	gold quality
epithelium of bronchus	UBERON:0002031	99.82	gold quality
mucosa of transverse colon	UBERON:0004991	99.81	gold quality
colonic mucosa	UBERON:0000317	99.73	gold quality
bronchus	UBERON:0002185	99.72	gold quality
mucosa of sigmoid colon	UBERON:0004993	99.69	gold quality
nasal cavity epithelium	UBERON:0005384	99.68	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	99.61	gold quality
rectum	UBERON:0001052	99.60	gold quality
ileal mucosa	UBERON:0000331	99.57	gold quality
metanephros cortex	UBERON:0010533	99.12	gold quality
right uterine tube	UBERON:0001302	98.09	gold quality
palpebral conjunctiva	UBERON:0001812	97.71	gold quality
left lobe of thyroid gland	UBERON:0001120	97.39	gold quality
trachea	UBERON:0003126	97.24	gold quality
right lobe of thyroid gland	UBERON:0001119	96.82	gold quality
thyroid gland	UBERON:0002046	96.44	gold quality
adult mammalian kidney	UBERON:0000082	96.32	gold quality
mucosa of paranasal sinus	UBERON:0005030	95.99	gold quality
epithelium of nasopharynx	UBERON:0001951	95.95	gold quality
nasal cavity mucosa	UBERON:0001826	95.57	gold quality
transverse colon	UBERON:0001157	94.76	gold quality
minor salivary gland	UBERON:0001830	94.66	gold quality
vermiform appendix	UBERON:0001154	94.60	gold quality
prostate gland	UBERON:0002367	94.38	gold quality
caput epididymis	UBERON:0004358	93.49	gold quality
small intestine Peyer’s patch	UBERON:0003454	93.13	gold quality
adult organism	UBERON:0007023	92.52	gold quality
body of stomach	UBERON:0001161	92.26	gold quality
gall bladder	UBERON:0002110	92.14	gold quality

Single-cell (SCXA)

Detected in 17 experiment(s), a significant marker in 16.

Experiment	Marker?	Max mean expression
E-GEOD-125970	yes	2935.72
E-MTAB-8410	yes	2930.72
E-HCAD-15	yes	2181.87
E-GEOD-130148	yes	2013.85
E-MTAB-10283	yes	1727.26
E-CURD-114	yes	61.64
E-MTAB-10287	yes	49.39
E-HCAD-1	yes	32.77
E-HCAD-10	yes	23.70
E-MTAB-6701	yes	20.91
E-HCAD-31	yes	19.35
E-MTAB-5061	yes	16.72
E-GEOD-81608	yes	16.45
E-ENAD-27	yes	10.37
E-MTAB-6678	yes	8.69

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

26 targeting TSPAN1, 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-6833-3P	100.00	70.63	3197
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-586	99.65	70.40	2051
HSA-MIR-6081	99.48	66.07	1446
HSA-MIR-1275	99.47	67.90	2749
HSA-MIR-361-3P	99.19	66.45	1381
HSA-MIR-6071	99.16	67.77	1780
HSA-MIR-194-5P	99.01	69.65	1465
HSA-MIR-491-3P	98.88	68.86	1224
HSA-MIR-629-5P	98.78	68.72	1032
HSA-MIR-4297	98.77	66.95	2013
HSA-MIR-4463	98.56	66.05	1071
HSA-MIR-93-3P	98.15	66.65	1309
HSA-MIR-197-3P	98.09	69.23	1004
HSA-MIR-6870-3P	98.08	65.10	692
HSA-MIR-33B-3P	97.92	67.39	529
HSA-MIR-515-3P	97.92	67.98	506
HSA-MIR-519E-3P	97.92	68.25	508
HSA-MIR-637	97.91	64.05	1517
HSA-MIR-6781-3P	97.44	66.85	970
HSA-MIR-2682-3P	97.10	66.16	840
HSA-MIR-6729-3P	96.91	66.79	703
HSA-MIR-6805-5P	95.79	64.86	670
HSA-MIR-4323	93.93	63.89	656
HSA-MIR-4732-5P	90.07	64.77	412

Literature-anchored findings (GeneRIF, showing 31)

• Overexpression of NET-1 is associated with undifferentiated squamous cell carcinoma of cervical neoplasms (PMID:12115476)
• Detection of NET-1 gene expression in liver biopsy may provide useful information about the biological behavior of hepatocellular carcinoma. (PMID:17913940)
• Overexpression of TSPAN1 and Ki67 was negatively correlated with carcinoma differentiation, and the overexpression of TSPAN1 and CD34 was positively correlated with infiltration and lymph node status of the tumor. (PMID:18822690)
• describe the generation of Tspan-1-specific antibodies and immunohistochemical staining of different subtypes of ovarian carcinomas that revealed significant differences in Tspan-1 expression that was pronounced in mucinous and endometrioid tumors (PMID:19017553)
• Data show that Tspan-1-EGFP expressed in ovarian carcinoma cells was detected mainly in lysosomes, but also in the plasma membrane and in the ER. (PMID:19508227)
• TSPAN1 may be another important breast cancer suppressor gene belonging to the tetraspanin superfamily. (PMID:20680643)
• The overexpression of Tspan-1 was found in HCC tissues, positively correlated with clinical stage and negatively correlated with survival rate. (PMID:20890423)
• RNAi-mediated downregulation of TSPAN1 expression significantly inhibits the proliferation and invasion of colon cancer cells in vitro. (PMID:21302622)
• These studies demonstrate for the first time that Tspan-1 is an interacting partner with human thiamine transporter-1 and that this interaction affects thiamine transporter-1 stability. (PMID:21836059)
• Study provided the gene expression profile of HBV-related HCC and presented differential expression patterns of SATB-1, TM4SF-1 and ST-14 between cancerous and noncancerous tissues in patients with HBV-related HCC. (PMID:22088470)
• data suggest that the NET-1 gene may play an important role in proliferation, migration and endocytosis in the development and progress of hepatocellular carcinoma (PMID:22378020)
• these data argue against a role for tetraspanin 1 as a genuine mediator of cell surface receptor signalling but rather document a role for tetraspanin 1 in the control of cervical cancer cell motility and invasion. (PMID:23754316)
• TSPAN1 was proved to induce migration, and so up-regulation of TSPAN1 by miR-200a may explain why over-expressing miR-200a promotes NSCLC cells migration (PMID:23938385)
• our current data demonstrate that miR-638 functions as a tumor suppressor in human colorectal carcinoma by inhibiting TSPAN1 (PMID:25301729)
• Restoration of TSPAN1 rescued the effects of miR-573 overexpression. Therefore, our findings suggest that the miR-573/TSPAN1 axis is important in the control of gastric carcinogenesis (PMID:26054975)
• The present study demonstrated that Tspan1 plays an important role in Pancreatic cancer carcinogenic progression, including migration and invasion. (PMID:26370588)
• TSPAN1 has a role in prostate cancer progression and is a marker for early biochemical recurrence after radical prostatectomy (PMID:27556508)
• miR4913p is frequently downregulated in OS. miR4913p suppressed OS cell growth and invasion. TSPAN1 was identified to be a novel target of miR4913p. Overexpressed TSPAN1 conferred OS cell growth and invasion. (PMID:28849017)
• Study found that tetraspanin-1 was significantly higher in acute T cell-mediated rejection (TCMR) patients and could be detected in urine of kidney transplant recipients which makes it s potential diagnostic protein for TCMR. (PMID:30226858)
• In accordance with the functional characteristics of the TSPAN superfamily, authors proved that TSPAN1 interacted with integrin alpha6beta1 to amplify the phosphoinositide-3-kinase (PI3K)/AKT/glycogen synthase kinase (GSK)-3beta/Snail family transcriptional repressor (Snail)/phosphatase and tensin homolog (PTEN) feedback loop. (PMID:30514341)
• In pancreatic cancer (PC) tissue samples expression of TSPAN1 was markedly increased compared to normal samples. siRNA knockdown of TSPAN1 in PC cell lines suppressed PC cell migration and invasion and downregulated MMP2 expression. Transfection with siRNA targeted to PLCgamma revealed that TSPAN1 siRNA suppressed PC cell migration and invasion, and MMP2 expression by blocking the translocation and phosphorylation of P… (PMID:30720116)
• Silencing tetraspanin 1 (TSPAN1) promotes the phosphorylation of Smad2 protein (Smad2)/Smad3 protein (Smad3) and stabilizes beta-catenin protein. (PMID:30869194)
• TSPAN1 promotes autophagy flux and mediates cooperation between WNT-CTNNB1 signaling and autophagy via the MIR454-FAM83A-TSPAN1 axis in pancreatic cancer. (PMID:32972302)
• Bioinformatics analysis reveals TSPAN1 as a candidate biomarker of progression and prognosis in pancreatic cancer. (PMID:33188589)
• miR-573 suppresses pancreatic cancer cell proliferation, migration, and invasion through targeting TSPAN1. (PMID:33320287)
• Tetraspanin 1 promotes endometriosis leading to ovarian clear cell carcinoma. (PMID:33331115)
• Prognostic role of TSPAN1, KIAA1324 and ESRP1 in prostate cancer. (PMID:33455017)
• Tetraspanin 1 (TSPAN1) promotes growth and transferation of breast cancer cells via mediating PI3K/Akt pathway. (PMID:34852709)
• The immunological characteristics of TSPAN1 expressing B cells in autoimmune hepatitis. (PMID:36591302)
• TSPAN1 inhibits metastasis of nasopharyngeal carcinoma via suppressing NF-kB signaling. (PMID:38135697)
• ALKBH5 Suppresses Autophagy in Prostate Cancer Cells via Inhibiting m6A-Modification of TSPAN1 mRNA. (PMID:38273746)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	tspan1	ENSDARG00000052027
mus_musculus	Tspan1	ENSMUSG00000028699
rattus_norvegicus	Tspan1	ENSRNOG00000023320

Paralogs (32): TSPAN6 (ENSG00000000003), CD9 (ENSG00000010278), TSPAN9 (ENSG00000011105), TSPAN17 (ENSG00000048140), TSPAN32 (ENSG00000064201), CD82 (ENSG00000085117), TSPAN15 (ENSG00000099282), CD37 (ENSG00000104894), UPK1A (ENSG00000105668), TSPAN12 (ENSG00000106025), TSPAN13 (ENSG00000106537), TSPAN14 (ENSG00000108219), CD81 (ENSG00000110651), TSPAN11 (ENSG00000110900), PRPH2 (ENSG00000112619), UPK1B (ENSG00000114638), TSPAN8 (ENSG00000127324), TSPAN16 (ENSG00000130167), TSPAN2 (ENSG00000134198), CD63 (ENSG00000135404), TSPAN31 (ENSG00000135452), TSPAN3 (ENSG00000140391), CD53 (ENSG00000143119), ROM1 (ENSG00000149489), TSPAN7 (ENSG00000156298), TSPAN18 (ENSG00000157570), TSPAN33 (ENSG00000158457), TSPAN5 (ENSG00000168785), CD151 (ENSG00000177697), TSPAN10 (ENSG00000182612), TSPAN4 (ENSG00000214063), TSPAN19 (ENSG00000231738)

Protein

Protein identifiers

Tetraspanin-1 — O60635 (reviewed: O60635)

Alternative names: Tetraspan NET-1, Tetraspanin TM4-C

All UniProt accessions (1): O60635

UniProt curated annotations — full annotation on UniProt →

Function. Structural component of specialized membrane microdomains known as tetraspanin-enriched microdomains (TERMs), which act as platforms for receptor clustering and signaling. Participates thereby in diverse biological functions such as cell signal transduction, adhesion, migration and protein trafficking. Regulates neuronal differentiation in response to NGF by facilitating NGF-mediated activation of NTRK1/TRKA receptor tyrosine kinase and subsequent downstream signaling pathways. Plays a role in the inhibition of TNFalpha-induced apoptosis. Mechanistically, inhibits the NF-kappa-B signaling pathway by blocking phosphorylation of CHUK. Also promotes the stability of the thiamine transporter 1/SLC19A2 in intestinal epithelial cells leading to an increase of thiamine uptake process.

Subunit / interactions. Interacts with SLC19A2. Interacts with NTRK1/TRKA.

Subcellular location. Cell membrane. Lysosome membrane.

Similarity. Belongs to the tetraspanin (TM4SF) family.

RefSeq proteins (1): NP_005718* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000301	Tetraspanin_animals	Family
IPR008952	Tetraspanin_EC2_sf	Homologous_superfamily
IPR018499	Tetraspanin/Peripherin	Family
IPR018503	Tetraspanin_CS	Conserved_site

Pfam: PF00335

UniProt features (21 total): topological domain 5, glycosylation site 4, mutagenesis site 4, transmembrane region 4, sequence variant 2, chain 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O60635-F1	88.31	0.74

Functional residue map

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

Glycosylation sites (4): 141, 154, 178, 184

Mutagenesis-validated functional residues (4):

Position	Phenotype
141	loss of glycosylation.
154	loss of glycosylation.
178	loss of glycosylation.
184	loss of glycosylation.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 168 (showing top): BUYTAERT_PHOTODYNAMIC_THERAPY_STRESS_DN, GOCC_VACUOLAR_MEMBRANE, YANG_BREAST_CANCER_ESR1_BULK_UP, ENK_UV_RESPONSE_KERATINOCYTE_UP, GOZGIT_ESR1_TARGETS_DN, GGGTGGRR_PAX4_03, GATA3_01, KIM_RESPONSE_TO_TSA_AND_DECITABINE_UP, SENGUPTA_NASOPHARYNGEAL_CARCINOMA_DN, GOBP_PROTEIN_STABILIZATION, GATA1_01, chr1p34, LUI_THYROID_CANCER_CLUSTER_5, SCHAEFFER_PROSTATE_DEVELOPMENT_12HR_UP, SCHAEFFER_PROSTATE_DEVELOPMENT_48HR_UP

GO Biological Process (1): protein stabilization (GO:0050821)

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

GO Cellular Component (10): nucleoplasm (GO:0005654), cytoplasm (GO:0005737), lysosomal membrane (GO:0005765), plasma membrane (GO:0005886), membrane (GO:0016020), cell junction (GO:0030054), vesicle (GO:0031982), perinuclear region of cytoplasm (GO:0048471), extracellular exosome (GO:0070062), lysosome (GO:0005764)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	5
regulation of protein stability	1
binding	1
nuclear lumen	1
intracellular anatomical structure	1
lysosome	1
lytic vacuole membrane	1
membrane	1
cell periphery	1
membrane-bounded organelle	1
cytoplasm	1
extracellular vesicle	1
lytic vacuole	1

Protein interactions and networks

STRING

918 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TSPAN1	TM4SF5	O14894	801
TSPAN1	TM4SF1	P30408	793
TSPAN1	SLC19A2	O60779	660
TSPAN1	CMTM1	Q8IZ96	570
TSPAN1	CDHR1	Q96JP9	565
TSPAN1	PTGFRN	Q9P2B2	560
TSPAN1	TSPAN13	O95857	523
TSPAN1	ITGB1	P05556	508
TSPAN1	TSPAN31	Q12999	506
TSPAN1	TM4SF18	Q96CE8	505
TSPAN1	CD19	P15391	456
TSPAN1	CD44	P16070	456
TSPAN1	CKLF	Q9UBR5	447
TSPAN1	CMTM2	Q8TAZ6	447
TSPAN1	CMTM5	Q96DZ9	445

IntAct

14 interactions, top by confidence:

A	B	Type	Score
TSPAN1	SLC19A2	psi-mi:“MI:0915”(physical association)	0.600
TSPAN1	SLC19A2	psi-mi:“MI:0403”(colocalization)	0.600
TSPAN1	TFAM	psi-mi:“MI:0915”(physical association)	0.560
TSPAN1	TMEM80	psi-mi:“MI:0915”(physical association)	0.560
NFKBIB	TSPAN1	psi-mi:“MI:0915”(physical association)	0.370
TSPAN1	TLCD2	psi-mi:“MI:0914”(association)	0.350
TSPAN1	TFAM	psi-mi:“MI:0915”(physical association)	0.000
TSPAN1	TMEM80	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (17): TSPAN1 (Two-hybrid), TMEM80 (Two-hybrid), EXTL2 (Affinity Capture-MS), CSGALNACT2 (Affinity Capture-MS), TLCD2 (Affinity Capture-MS), FAM134C (Affinity Capture-MS), MTCH2 (Affinity Capture-MS), TMEM186 (Affinity Capture-MS), CD9 (Affinity Capture-MS), ULBP3 (Affinity Capture-MS), C10orf35 (Affinity Capture-MS), SNX13 (Affinity Capture-MS), FAM210B (Affinity Capture-MS), ZFPL1 (Affinity Capture-MS), ALG14 (Affinity Capture-MS)

ESM2 similar proteins: O00322, O42281, O42282, O42581, O42582, O42583, O46101, O60635, O70352, O95859, P15499, P17438, P17810, P23942, P27701, P35906, P38572, P40237, P52204, P58418, Q11098, Q29RH7, Q2KIS9, Q3T0S3, Q4R7W6, Q4V922, Q504G0, Q569A2, Q5CZV0, Q5M962, Q5R8B5, Q5RC27, Q6AYR9, Q6GPA5, Q6NUZ2, Q6NWG0, Q6P1U2, Q6ZUX7, Q7T392, Q7TQI0

Diamond homologs: A0A8M2B5N2, A0A8V0ZLT4, B0BM39, B3VSC2, B5X3I6, O14817, O60635, O75954, O97703, P11049, P60033, P60034, Q06AA5, Q11098, Q26499, Q3T0S3, Q4R7W6, Q4V8E0, Q58CY8, Q5RAP3, Q5RC27, Q61470, Q6AYR9, Q6DCQ3, Q6GMK6, Q80WR1, Q8BJU2, Q922J6, Q96SJ8, Q99J59, Q9DCK3, O60636, P19397, P24485, P30932, P35762, P40240, P62079, P62080, Q17QJ5

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	22
Likely pathogenic	28
Uncertain significance	162
Likely benign	228
Benign	9

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1072341	NM_017739.4(POMGNT1):c.595C>T (p.Gln199Ter)	Pathogenic
1366354	NM_017739.4(POMGNT1):c.1841T>A (p.Leu614Ter)	Pathogenic
1373868	NM_017739.4(POMGNT1):c.564_576del (p.Thr188_Ala189insTer)	Pathogenic
1458674	NM_017739.4(POMGNT1):c.1043dup (p.Ala349fs)	Pathogenic
2105374	NM_017739.4(POMGNT1):c.1812del (p.Arg605fs)	Pathogenic
2121735	NM_017739.4(POMGNT1):c.1436del (p.Met479fs)	Pathogenic
254272	NM_017739.4(POMGNT1):c.466G>A (p.Glu156Lys)	Pathogenic
2921808	NM_017739.4(POMGNT1):c.1780del (p.Ala594fs)	Pathogenic
2922731	NM_017739.4(POMGNT1):c.1829del (p.Gly610fs)	Pathogenic
2937722	NM_017739.4(POMGNT1):c.699del (p.Trp234fs)	Pathogenic
2942048	NM_017739.4(POMGNT1):c.426del (p.His142fs)	Pathogenic
2947427	NM_017739.4(POMGNT1):c.1725_1726del (p.Val576fs)	Pathogenic
4794306	NM_017739.4(POMGNT1):c.706del (p.Asp236fs)	Pathogenic
4815903	NM_017739.4(POMGNT1):c.1895+2T>C	Pathogenic
550363	NM_017739.4(POMGNT1):c.1104_1105del (p.Gln370fs)	Pathogenic
550917	NM_017739.4(POMGNT1):c.1604+2T>C	Pathogenic
552466	NM_017739.4(POMGNT1):c.1852A>T (p.Lys618Ter)	Pathogenic
56583	NM_017739.4(POMGNT1):c.1539+1G>T	Pathogenic
56586	NM_017739.4(POMGNT1):c.1738C>T (p.Arg580Ter)	Pathogenic
56587	NM_017739.4(POMGNT1):c.1769G>A (p.Trp590Ter)	Pathogenic
56604	NM_017739.4(POMGNT1):c.643C>T (p.Arg215Ter)	Pathogenic
970328	NM_017739.4(POMGNT1):c.1282C>T (p.Gln428Ter)	Pathogenic
1067007	NM_017739.4(POMGNT1):c.1813C>A (p.Arg605Ser)	Likely pathogenic
1493214	NM_017739.4(POMGNT1):c.1212-1G>A	Likely pathogenic
1526402	NM_017739.4(POMGNT1):c.1286G>T (p.Gly429Val)	Likely pathogenic
1725088	NM_017739.4(POMGNT1):c.1117A>T (p.Lys373Ter)	Likely pathogenic
1984439	NM_017739.4(POMGNT1):c.1343G>A (p.Gly448Glu)	Likely pathogenic
2677977	NM_017739.4(POMGNT1):c.1398G>A (p.Trp466Ter)	Likely pathogenic
2938074	NM_017739.4(POMGNT1):c.1111-1G>A	Likely pathogenic
2943187	NM_017739.4(POMGNT1):c.1110+1G>T	Likely pathogenic

SpliceAI

1264 predictions. Top by Δscore:

Variant	Effect	Δscore
1:46184190:GCTGT:G	acceptor_gain	1.0000
1:46184592:A:AG	acceptor_gain	1.0000
1:46184593:G:GG	acceptor_gain	1.0000
1:46184880:AGGG:A	donor_gain	1.0000
1:46184881:GGG:G	donor_gain	1.0000
1:46184881:GGGG:G	donor_gain	1.0000
1:46184882:GG:G	donor_gain	1.0000
1:46184882:GGG:G	donor_gain	1.0000
1:46184883:GG:G	donor_gain	1.0000
1:46184884:G:GG	donor_gain	1.0000
1:46184885:T:A	donor_loss	1.0000
1:46185110:G:GG	donor_gain	1.0000
1:46185112:AGAGG:A	donor_loss	1.0000
1:46185116:G:GA	donor_loss	1.0000
1:46185117:T:A	donor_loss	1.0000
1:46185220:T:TA	acceptor_gain	1.0000
1:46185220:TGAAG:T	acceptor_loss	1.0000
1:46185222:AAG:A	acceptor_gain	1.0000
1:46185223:A:AC	acceptor_loss	1.0000
1:46185223:A:AG	acceptor_gain	1.0000
1:46185223:AG:A	acceptor_gain	1.0000
1:46185223:AGG:A	acceptor_gain	1.0000
1:46185224:G:A	acceptor_gain	1.0000
1:46185224:G:GC	acceptor_gain	1.0000
1:46185224:GGG:G	acceptor_gain	1.0000
1:46185224:GGGT:G	acceptor_gain	1.0000
1:46185224:GGGTT:G	acceptor_gain	1.0000
1:46185309:G:C	donor_loss	1.0000
1:46185310:T:A	donor_loss	1.0000
1:46176284:ATGGC:A	donor_gain	0.9900

AlphaMissense

1595 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:46184994:T:G	F158C	0.998
1:46184863:T:A	W140R	0.996
1:46184863:T:C	W140R	0.996
1:46184972:G:T	G151C	0.995
1:46184994:T:C	F158S	0.995
1:46184969:T:A	C150S	0.994
1:46184970:G:C	C150S	0.994
1:46184993:T:C	F158L	0.994
1:46184995:T:A	F158L	0.994
1:46184995:T:G	F158L	0.994
1:46185041:T:A	C174S	0.994
1:46185042:G:C	C174S	0.994
1:46184865:G:C	W140C	0.993
1:46184865:G:T	W140C	0.993
1:46184966:T:A	C149S	0.993
1:46184967:G:C	C149S	0.993
1:46185228:T:A	C200S	0.993
1:46185229:G:C	C200S	0.993
1:46185291:G:A	G221R	0.993
1:46185291:G:C	G221R	0.993
1:46184218:G:C	G29R	0.992
1:46185225:G:T	G199C	0.992
1:46184219:G:A	G29D	0.991
1:46184966:T:C	C149R	0.991
1:46184973:G:A	G151D	0.991
1:46184970:G:A	C150Y	0.990
1:46185041:T:C	C174R	0.990
1:46185043:T:G	C174W	0.990
1:46185286:C:A	A219E	0.990
1:46185292:G:A	G221E	0.990

dbSNP variants (sampled 300 via entrez): RS1000053163 (1:46176126 T>C), RS1000071848 (1:46185777 C>T), RS1000104135 (1:46183034 C>A,G,T), RS1000168804 (1:46195345 G>A), RS1000624006 (1:46182730 TAG>T), RS1000804489 (1:46176440 C>T), RS1000851011 (1:46196382 G>A), RS1001006969 (1:46188235 T>G), RS1001153534 (1:46176708 G>T), RS1001388776 (1:46195757 G>A,C), RS1001454678 (1:46176635 G>A,C), RS1001782757 (1:46190091 G>A), RS1001791600 (1:46175773 C>T), RS1001815333 (1:46189790 G>A,C), RS1002020059 (1:46181427 G>T)

Disease associations

OMIM: gene MIM:613170 | disease phenotypes: MIM:613151, MIM:613157, MIM:253280, MIM:617123, MIM:253600, MIM:261600, MIM:268000, MIM:608840

GenCC curated gene-disease

Mondo (12): muscular dystrophy-dystroglycanopathy (congenital with intellectual disability), type B3 (MONDO:0013155), autosomal recessive limb-girdle muscular dystrophy type 2O (MONDO:0013161), muscle-eye-brain disease (MONDO:0018939), muscular dystrophy-dystroglycanopathy (MONDO:0018276), muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A3 (MONDO:0009667), retinitis pigmentosa 76 (MONDO:0014929), autosomal recessive limb-girdle muscular dystrophy (MONDO:0015152), inherited retinal dystrophy (MONDO:0019118), phenylketonuria (MONDO:0009861), retinitis pigmentosa (MONDO:0019200), intellectual disability (MONDO:0001071), muscular dystrophy-dystroglycanopathy type B6 (MONDO:0012138)

Orphanet (10): POMGNT1-related limb-girdle muscular dystrophy R15 (Orphanet:206564), Muscle-eye-brain disease (Orphanet:588), Walker-Warburg syndrome (Orphanet:899), Congenital muscular dystrophy due to dystroglycanopathy (Orphanet:370953), Autosomal recessive limb-girdle muscular dystrophy (Orphanet:102015), OBSOLETE: Inherited retinal disorder (Orphanet:71862), Phenylketonuria (Orphanet:716), Retinitis pigmentosa (Orphanet:791), NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658), Congenital muscular dystrophy type 1D (Orphanet:98894)

HPO phenotypes

1 total (1 of 1 shown, HPO-id order):

HPO	Term
HP:0000556	Retinal dystrophy

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST005951_37	Body mass index	8.000000e-10

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004340	body mass index

MeSH disease descriptors (6)

Descriptor	Name	Tree numbers
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539
D010661	Phenylketonurias	C10.228.140.163.100.687; C16.320.565.100.766; C16.320.565.189.687; C18.452.132.100.687; C18.452.648.100.766; C18.452.648.189.687
D058499	Retinal Dystrophies	C11.768.585.658
D012174	Retinitis Pigmentosa	C11.270.684; C11.768.585.658.500; C16.320.290.684
C538640	Limb-girdle muscular dystrophy autosomal recessive (supp.)
C563844	Muscular Dystrophy, Congenital, Type 1D (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Ethinyl Estradiol	affects expression, decreases expression	3
sodium arsenite	decreases expression, affects cotreatment, increases abundance	2
(+)-JQ1 compound	decreases expression	2
Air Pollutants	decreases expression, increases abundance, increases expression	2
Estradiol	affects cotreatment, decreases expression, increases expression	2
Smoke	decreases expression, increases abundance, increases expression	2
Aflatoxin B1	decreases methylation, increases expression	2
aristolochic acid I	decreases expression	1
OTX015	decreases expression	1
mivebresib	decreases expression	1
dicrotophos	decreases expression	1
pirinixic acid	decreases expression, increases activity, affects binding	1
bisphenol A	affects expression	1
lead acetate	decreases expression	1
beta-lapachone	increases expression	1
cupric chloride	decreases expression	1
S-(1,2-dichlorovinyl)cysteine	affects cotreatment, increases expression	1
avobenzone	increases expression	1
perfluorooctane sulfonic acid	increases expression	1
monomethylarsonous acid	decreases expression	1
jinfukang	affects cotreatment, increases expression	1
NSC 689534	increases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Sunitinib	decreases expression	1
Arsenic	affects cotreatment, decreases expression, increases abundance	1
Atrazine	increases expression	1
Benzo(a)pyrene	affects methylation, decreases methylation, increases methylation	1
Calcitriol	increases expression	1
Camptothecin	increases expression	1
Cisplatin	affects cotreatment, increases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT01082328	PHASE4	COMPLETED	Response to Kuvan® in Subjects With Phenylketonuria (PKU) in a 4 Weeks Testing Period
NCT01617070	PHASE4	COMPLETED	Effects of Kuvan on Melatonin Secretion
NCT01965912	PHASE4	COMPLETED	Kuvan®’s Effect on the Cognition of Children With Phenylketonuria
NCT02677870	PHASE4	COMPLETED	The Effectiveness of Kuvan in Amish PKU Patients
NCT03788343	PHASE4	COMPLETED	Phenylalanine and Its Impact on Cognition
NCT04227080	PHASE4	UNKNOWN	BH4 Responsiveness in PAH Deficiency PKU Patients
NCT06780332	PHASE4	ACTIVE_NOT_RECRUITING	Rapid Drug Desensitization Study in Adults Experiencing Hypersensitivity Reactions to Palynziq
NCT06901323	PHASE4	ACTIVE_NOT_RECRUITING	Effect of L-carnitine Supplementation on Phenylalanine and Brain-derived Neurotrophic Factor Levels in Infants and Children With Phenylketonuria
NCT07477691	PHASE4	NOT_YET_RECRUITING	Immune Modulation During Palynziq® Treatment in Adults (IMPALA)
NCT00717080	PHASE4	COMPLETED	The Role of Capsular Tension Ring (CTR) in Anterior Capsular Contraction
NCT04224207	PHASE3	COMPLETED	Management of Retinitis Pigmentosa by Mesenchymal Stem Cells by Wharton’s Jelly Derived Mesenchymal Stem Cells
NCT07082855	PHASE3	NOT_YET_RECRUITING	A Multicenter, Randomized, Double-Blind, Controlled Clinical Study of Minocycline for the Treatment of Retinitis Pigmentosa
NCT00104247	PHASE3	COMPLETED	Study to Evaluate the Safety and Efficacy of Phenoptin™ in Subjects With Phenylketonuria Who Have Elevated Phenylalanine Levels
NCT00225615	PHASE3	COMPLETED	A Phase 3, Multicenter, Open-Label Extension Study of Phenoptin in Subjects With PKU Who Have Elevated Phenylalanine Levels
NCT00272792	PHASE3	COMPLETED	Study of Phenoptin to Increase Phenylalanine Tolerance in Phenylketonuric Children on a Phenylalanine-restricted Diet
NCT00332189	PHASE3	COMPLETED	Study of Phenoptin in Subjects With Phenylketonuria Who Participated in Protocols PKU-004 or PKU-006
NCT00838435	PHASE3	COMPLETED	Effect of Kuvan on Neurocognitive Function, Blood Phenylalanine Level, Safety, and Pharmacokinetics in Children With PKU
NCT01114737	PHASE3	COMPLETED	Safety and Therapeutic Effects of Sapropterin Dihydrochloride on Neuropsychiatric Symptoms in Phenylketonuria (PKU) Patients
NCT01376908	PHASE3	COMPLETED	Kuvan® in Phenylketonuria Patients Less Than 4 Years Old
NCT01732471	PHASE3	COMPLETED	Phase 3 Open-label Study to Evaluate the Response and Safety of Kuvan® in Subjects With Phenylketonuria
NCT01819727	PHASE3	COMPLETED	An Open-Label Phase 3 Study of BMN 165 for Adults With PKU Not Previously Treated w/ BMN 165
NCT01889862	PHASE3	COMPLETED	Phase 3 Study to Evaluate the Efficacy & Safety of Self-Administered Injections of BMN165 by Adults With PKU
NCT03694353	PHASE3	COMPLETED	Safety and Efficacy of Self Administered Injections of Pegvaliase (>40mg/Day Dose) in Adults With PKU
NCT05099640	PHASE3	COMPLETED	A Study of PTC923 in Participants With Phenylketonuria
NCT05166161	PHASE3	ACTIVE_NOT_RECRUITING	A Long-Term Safety Study of PTC923 in Participants With Phenylketonuria
NCT05270837	PHASE3	ACTIVE_NOT_RECRUITING	Study to Evaluate the Safety and Efficacy of Pegvaliase in Adolescents (Ages 12-17) With Phenylketonuria
NCT05764239	PHASE3	TERMINATED	Efficacy and Safety of SYNB1934 in Patients With PKU (SYNPHENY-3)
NCT06302348	PHASE3	RECRUITING	A Study of Sepiapterin in Participants With Phenylketonuria (PKU)
NCT06628128	PHASE3	RECRUITING	A Long-Term Study of JNT-517 in Participants With Phenylketonuria
NCT06971731	PHASE3	RECRUITING	A Study of JNT-517 in Participants With Phenylketonuria (PKU)
NCT00000114	PHASE3	COMPLETED	Randomized Trial of Vitamin A and Vitamin E Supplementation for Retinitis Pigmentosa
NCT00000116	PHASE3	COMPLETED	Randomized Trial of DHA for Retinitis Pigmentosa Patients Receiving Vitamin A
NCT00346333	PHASE3	COMPLETED	Clinical Trial of Lutein for Patients With Retinitis Pigmentosa Receiving Vitamin A
NCT01786395	PHASE3	TERMINATED	Phase III Efficacy and Safety Clinical Study of UF-021 for Treatment of Retinitis Pigmentosa
NCT04636853	PHASE3	COMPLETED	CB-PRP in Retinitis Pigmentosa and Dry Age-related Macular Degeneration
NCT05537220	PHASE3	ACTIVE_NOT_RECRUITING	Oral N-acetylcysteine for Retinitis Pigmentosa
NCT05800301	PHASE3	COMPLETED	Management of Retinitis Pigmentosa Via Combination of Wharton’s Jelly-derived Mesenchymal Stem Cells and Magnovision
NCT05926583	PHASE3	ACTIVE_NOT_RECRUITING	A Study of AAV5-hRKp.RPGR for the Treatment of Japanese Participants With X-linked Retinitis Pigmentosa
NCT06388200	PHASE3	ACTIVE_NOT_RECRUITING	A Phase 3 Study Of OCU400 Gene Therapy for the Treatment Of Retinitis Pigmentosa
NCT07290530	PHASE3	NOT_YET_RECRUITING	24-Month Trial of NPI-001 for the Preservation of Photoreceptors in Retinitis Pigmentosa Associated With Usher Syndrome