TKTL1

Summary

TKTL1 (transketolase like 1, HGNC:11835) is a protein-coding gene on chromosome Xq28, encoding Transketolase-like protein 1 (P51854). Catalyzes the transfer of a two-carbon ketol group from a ketose donor to an aldose acceptor, via a covalent intermediate with the cofactor thiamine pyrophosphate.

The protein encoded by this gene is a transketolase that acts as a homodimer and catalyzes the conversion of sedoheptulose 7-phosphate and D-glyceraldehyde 3-phosphate to D-ribose 5-phosphate and D-xylulose 5-phosphate. This reaction links the pentose phosphate pathway with the glycolytic pathway. Variations in this gene may be the cause of Wernicke-Korsakoff syndrome. Three transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 8277 — RefSeq curated summary.

At a glance

• GWAS associations: 8
• Clinical variants (ClinVar): 119 total
• MANE Select transcript: NM_012253

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11835
Approved symbol	TKTL1
Name	transketolase like 1
Location	Xq28
Locus type	gene with protein product
Status	Approved
Aliases	TKR, TKT2
Ensembl gene	ENSG00000007350
Ensembl biotype	protein_coding
OMIM	300044
Entrez	8277

Gene structure

Transcript identifiers

Ensembl transcripts: 9 — 4 protein_coding, 3 protein_coding_CDS_not_defined, 2 nonsense_mediated_decay

ENST00000369912, ENST00000369915, ENST00000426203, ENST00000426989, ENST00000439635, ENST00000463884, ENST00000465168, ENST00000482044, ENST00000710264

RefSeq mRNA: 3 — MANE Select: NM_012253 NM_001145933, NM_001145934, NM_012253

CCDS: CCDS35448, CCDS55541

Canonical transcript exons

ENST00000369915 — 13 exons

Exon	Start	End
ENSE00000678229	154309345	154309442
ENSE00000678233	154310836	154311027
ENSE00001683721	154325339	154325422
ENSE00001731288	154312580	154312773
ENSE00001748564	154315173	154315337
ENSE00001925446	154295795	154295993
ENSE00003551688	154305304	154305421
ENSE00003559220	154323207	154323337
ENSE00003567459	154320757	154320913
ENSE00003650214	154311111	154311238
ENSE00004010788	154327591	154327687
ENSE00004010789	154327839	154327958
ENSE00004010790	154329516	154330350

Expression profiles

Bgee: expression breadth ubiquitous, 164 present calls, max score 98.41.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 1.1821 / max 416.3514, expressed in 125 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
198127	0.8984	20
198128	0.1700	62
198131	0.0980	46
198132	0.0157	8

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	98.41	gold quality
right testis	UBERON:0004534	98.17	gold quality
left testis	UBERON:0004533	97.30	gold quality
adult organism	UBERON:0007023	97.29	gold quality
testis	UBERON:0000473	96.07	gold quality
ventricular zone	UBERON:0003053	94.08	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	91.82	gold quality
male germ cell	CL:0000015	90.75	gold quality
sperm	CL:0000019	90.51	gold quality
heart right ventricle	UBERON:0002080	89.00	gold quality
left ventricle myocardium	UBERON:0006566	87.51	gold quality
ganglionic eminence	UBERON:0004023	87.27	gold quality
myocardium	UBERON:0002349	83.88	silver quality
cardiac muscle of right atrium	UBERON:0003379	80.15	silver quality
granulocyte	CL:0000094	79.74	gold quality
heart left ventricle	UBERON:0002084	78.17	gold quality
cardiac ventricle	UBERON:0002082	78.16	gold quality
oocyte	CL:0000023	76.31	gold quality
embryo	UBERON:0000922	76.10	gold quality
blood	UBERON:0000178	75.80	gold quality
apex of heart	UBERON:0002098	73.61	gold quality
heart	UBERON:0000948	73.25	gold quality
cardiac atrium	UBERON:0002081	73.12	gold quality
right atrium auricular region	UBERON:0006631	72.82	gold quality
buccal mucosa cell	CL:0002336	71.03	gold quality
secondary oocyte	CL:0000655	70.87	gold quality
diaphragm	UBERON:0001103	68.40	gold quality
frontal pole	UBERON:0002795	62.86	gold quality
middle frontal gyrus	UBERON:0002702	62.73	gold quality
paraflocculus	UBERON:0005351	62.49	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-GEOD-124263	yes	1518.08
E-GEOD-134144	yes	1223.25
E-ANND-3	no	2.47

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): HIF1A

miRNA regulators (miRDB)

30 targeting TKTL1, 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-1252-5P	100.00	69.80	2774
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-3143	99.93	71.96	3104
HSA-MIR-605-3P	99.88	69.22	1833
HSA-MIR-4698	99.84	71.41	4303
HSA-MIR-448	99.79	72.37	2103
HSA-MIR-4645-3P	99.76	69.33	993
HSA-MIR-1249-5P	99.61	66.55	2049
HSA-MIR-6797-5P	99.61	66.55	2084
HSA-MIR-4261	99.59	70.30	3415
HSA-MIR-203A-3P	99.49	70.56	2806
HSA-MIR-542-3P	99.34	67.58	1270
HSA-MIR-5190	99.15	67.76	1234
HSA-MIR-371A-5P	99.08	66.51	1914
HSA-MIR-8066	99.05	68.66	1532
HSA-MIR-6814-5P	99.03	66.68	1273
HSA-MIR-361-5P	98.95	70.16	1340
HSA-MIR-4477A	98.83	69.75	2952
HSA-MIR-4501	98.72	67.19	921
HSA-MIR-5187-5P	98.54	67.94	952
HSA-MIR-640	98.44	66.93	644
HSA-MIR-6757-5P	98.08	65.50	724
HSA-MIR-1255B-2-3P	97.80	67.04	880
HSA-MIR-645	97.28	66.30	486
HSA-MIR-6515-5P	97.08	65.48	1219
HSA-MIR-8069	97.05	66.79	718
HSA-MIR-555	95.92	65.25	564
HSA-MIR-4694-5P	94.62	65.39	532
HSA-MIR-6716-3P	93.66	73.42	51
HSA-MIR-3186-5P	87.11	67.29	51

Literature-anchored findings (GeneRIF, showing 40)

• demonstrate the presence of a second transketolase enzyme (TKTL1) in humans. This protein and its mutations and clinical implications are characterized. (PMID:15991799)
• Findings strongly indicate that overexpression of TKTL1 is responsible for observed tumor-specific effects of transketolase enzyme reactions (PMID:16465194)
• TKTL1 upregulation is a common phenomenon in gastric cancer and cancer of the gastroesophageal junction leading to an enhanced, oxygen-independent glucose usage which might contribute to a more aggressive tumor growth (PMID:16969476)
• RNAi-mediated suppression of TKTL1 in hepatoma cells significantly reduces total transketolase activity and inhibits proliferation. Findings suggest that TKTL1 plays an important role in glycometabolism and cell cycle progression in tumors. (PMID:17321041)
• These results indicate that TKTL1 gene influences total transketolase activity and cell proliferation in human hepatoma cells. (PMID:17321041)
• Transketolase, but not G6PD activity, was more elevated in metastasizing tumors and TKTL1 protein was significantly overexpressed in progressing tumors (p = 0.03). (PMID:18302154)
• expression of transketolase-like enzyme 1 was found in 81% of granulosa cell tumors of the ovary (PMID:18394773)
• Compared with grades II and III astrocytic gliomas, glioblastoma multiformes showed higher expression of TKTL1, more positive tumors, and a higher percentage of positive tumor cells. (PMID:18550470)
• findings suggest that tktl1 overexpression in thyroid carcinoma is a factor which facilitates tumor growth and progression (PMID:18615628)
• results suggest that both Transketolase-like enzyme 1 (TKTL1) and p-Akt protein play an important role in the progression of cervical neoplasia (PMID:18686341)
• TKTL1 overexpression may be considered not only as a new tumor marker but also as a good target for anticancer therapy. (PMID:19065656)
• TKTL1 plays an important role in total transketolase activity and cells proliferation in uterine cervix cancer (PMID:19331662)
• Expression of pAkt, GLUT1 and TKTL1 were higher in breast cancer and DCIS than in normal tissue. (PMID:19655166)
• TKTL1 is a novel candidate oncogene that is epigenetically activated by aberrant hypomethlation and contributes to a malignant phenotype through altered glycolytic metabolism and HIF1alpha accumulation. (PMID:20103683)
• Overexpression of TKTL1 is associated with gastric cancer. (PMID:20200485)
• LDH5 is overexpressed in non-small cell lung cancer and could serve as a marker for malignancy. LDH5 correlates positively with the prognostic marker transketolase like 1 protein. (PMID:20385008)
• transketolase-like 1 protein (TKTL1) is expressed in human endometrial cancer (PMID:20592357)
• TKTL1 does not regulate glucose metabolism in malignant cells. (PMID:20596653)
• Single Nucleotide Polymorphism in TKTL1 is associated with diabetic nephropathy. (PMID:20826743)
• Transketolase-like protein 1 confers resistance to serum withdrawal in vitro. (PMID:20884117)
• Investigated the expression of VEGFR-1, VEGFR-2 and TKTL1 in patients with LARC treated with neoadjuvant chemoradiotherapy and cetuximab. High TKTL1 expression significantly correlated with disease free survival. (PMID:21854597)
• correlation of TKTL expression with tumor stage, probability of tumor recurrence and survival in colorectal cancer (PMID:21980427)
• TKTL1 overexpression is a new and independent predictor of survival for patients with non-small cell lung cancer (PMID:22027741)
• TKTL1 could be a target protein for improved therapeutic strategies in some cases of lung cancer. (PMID:22445516)
• TKTL1 is dysregulated in malignant tumors of the ocular adnexa, and enhanced expression seems to predict clinical outcome, especially the tumor recurrence rate. (PMID:22658715)
• TKLT1 is devoid of two critical histidine residues that are conserved in other TK. (PMID:22803947)
• No transketolase activity of TKTDelta38 can be detected for conversion of physiological sugar substrates thus arguing against an intrinsically encoded enzymatic function of TKTL1 in tumor cell metabolism (PMID:23118983)
• EDIM-TKTL1 blood test revealed good concordance with FDG-PET/CT results in patients with malignancies demonstrating its efficacy to detect upregulation of glucose metabolism in primary tumors or metastases. (PMID:23130932)
• Data indicate that transketolase (hTKT). shares 61% sequence identity with transketolase-like protein (TKTL1). (PMID:23261987)
• In 50% of colorectal cancer patients, TKTL1 protein expression was upregulated in tumor compared to non-tumor tissue. TKTL1 expression correlated with HIF-1alpha protein expression and was induced upon hypoxic conditions. (PMID:24193262)
• DNASEX and TKTL1 detection in patient blood is associated with poor disease-free survival rate in oral squamous cell carcinoma. (PMID:24304513)
• TKTL1 expression levels appear to decline in the course of CML with lowest levels during blast crisis. A potential reason is a shift of TKTL1-high-expressing mature granulocytes towards TKTL1-low-expressing immature cells and blasts. (PMID:24390277)
• the cytoplasmatic expression of TKTL1 is specific for MIBC tissue compared with histopathologically benign urothelium. (PMID:25572961)
• our results suggest that TKTL1 as a key prognostic factor may be a novel target for therapy of the patients with esophageal squamous cell carcinoma. (PMID:26032094)
• Data revealed exceptional occurrence of TKTL1 in a panel of malignant human cell lines in vitro suggesting that its presence was unrelated to either the rate of glucose consumption/lactic acid production or resistance against chemo- and radiotherapy. (PMID:26187043)
• TKTL1 is associated with a more aggressive behavior in human esophageal squamous cell carcinoma cells (PMID:26349965)
• Both TKTL1 and p63 are independent prognostic factors of the poor outcome of gastric cancer patients (PMID:26406948)
• We show that high TKTL1 in tumor tissue can lead to poor survival in colorectal cancer. TKTL1 thus can serve as a candidate marker for identifying patients at risk of recurrent disease (PMID:26650256)
• Data provide evidence for an important role of TKTL1 in aerobic glycolysis and tumor promotion in melanoma that may result from defective promoter methylation. (PMID:26907172)
• Knockdown of TKTL1 additively complements cisplatin-induced cytotoxicity in the nasopharyngeal carcinoma cells by inhibiting the levels of NADPH and ribose-5-phosphate, indicating that TKTL1 may be a promising target to improve the therapeutic effect combining with cisplatin for the patients with nasopharyngeal carcinoma. (PMID:27916418)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
mus_musculus	Tktl1	ENSMUSG00000031397
rattus_norvegicus	Tktl1	ENSRNOG00000055557
drosophila_melanogaster	CG5103	FBGN0036784
drosophila_melanogaster	CG8036	FBGN0037607
caenorhabditis_elegans		WBGENE00008506

Paralogs (4): BCKDHB (ENSG00000083123), TKTL2 (ENSG00000151005), TKT (ENSG00000163931), PDHB (ENSG00000168291)

Protein

Protein identifiers

Transketolase-like protein 1 — P51854 (reviewed: P51854)

Alternative names: Transketolase 2, Transketolase-related protein

All UniProt accessions (5): P51854, A0AA34QVR6, A2ID95, F8WF97, H0Y808

UniProt curated annotations — full annotation on UniProt →

Function. Catalyzes the transfer of a two-carbon ketol group from a ketose donor to an aldose acceptor, via a covalent intermediate with the cofactor thiamine pyrophosphate. During fetal neocortex development, may be essential to maintain the full number of basal radial glia (bRG). bRG are neural progenitor cells that undergo asymmetric divisions, generating a bRG (self-renewal) and a neuron, in contrast to basal intermediate progenitors (bIPs), which typically divide once to give rise to 2 neurons. bRG generate more cortical neurons over time than bIPs.

Subunit / interactions. Homodimer.

Subcellular location. Cytoplasm.

Tissue specificity. Widely expressed. Expressed in endothelial cells and in peripheral neurons (at protein level). Not expressed in fetal neocortex. Expressed in fetal neocortex.

Cofactor. Binds 1 Mg(2+) ion per subunit. Can also utilize other divalent metal cations, such as Ca(2+), Mn(2+) and Co(2+). Binds 1 thiamine pyrophosphate per subunit.

Polymorphism. Variant Lys-317 is typically present in extinct archaic humans, Neanderthals and Denisovans, as well as in other primates. It is rare in modern human population with a frequency of 0.03%. No homozygote is reported in the Genome Aggregation Database (gnomAD v2.1.1). The modern human variant Arg-317 is thought to lead to a greater neocortical neurogenesis compared to archaic human Lys-317, in particular in the frontal lobe. It is currently unknown if the presence of variant Lys-317 in modern humans is associated with a disease or has any effect on cognitive skills.

Similarity. Belongs to the transketolase family.

Isoforms (3)

UniProt ID	Names	Canonical?
P51854-3	3, Long	yes
P51854-1	2
P51854-4	4, Short

RefSeq proteins (3): NP_001139405, NP_001139406, NP_036385* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR005474	Transketolase_N	Domain
IPR005475	Transketolase-like_Pyr-bd	Domain
IPR009014	Transketo_C/PFOR_II	Homologous_superfamily
IPR020826	Transketolase_BS	Binding_site
IPR029061	THDP-binding	Homologous_superfamily
IPR033248	Transketolase_C	Domain
IPR051424	Transketolase-like	Family

Pfam: PF00456, PF02779, PF02780

Enzyme classification (BRENDA):

• EC 2.2.1.1 — transketolase (BRENDA: 41 organisms, 197 substrates, 77 inhibitors, 215 Km, 72 kcat entries)

Substrate kinetics (BRENDA)

38 substrates with measured Km, best-characterized 15. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
D-XYLULOSE 5-PHOSPHATE	0.0056–4.08	62
D-RIBOSE 5-PHOSPHATE	0.007–7	52
THIAMINE DIPHOSPHATE	0.0003–0.007	14
FRUCTOSE 6-PHOSPHATE	0.0002–11	11
GLYCOLALDEHYDE	0.13–200	8
HYDROXYPYRUVATE	—	7
D-FRUCTOSE 6-PHOSPHATE	0.029–0.72	6
3-FORMYLBENZOIC ACID	1.3–56	5
D-ERYTHROSE 4-PHOSPHATE	0.023–0.36	5
4-FORMYLBENZOIC ACID	13–251	4
XYLULOSE 5-PHOSPHATE	0.0004–0.16	4
3-HYDROXYBENZALDEHYDE	180–390	3
D-RIBOSE-5-PHOSPHATE	0.13–2.75	3
L-ERYTHRULOSE	4.9–8	3
SEDOHEPTULOSE 7-PHOSPHATE	0.031–4	3

Catalyzed reactions (Rhea), 1 shown:

• D-sedoheptulose 7-phosphate + D-glyceraldehyde 3-phosphate = aldehydo-D-ribose 5-phosphate + D-xylulose 5-phosphate (RHEA:10508)

UniProt features (30 total): binding site 19, sequence variant 3, site 2, splice variant 2, sequence conflict 2, chain 1, active site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P51854-F1	94.74	0.89

Functional residue map

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

Catalytic / active sites (3): 340 (proton donor); 46 (important for catalytic activity); 232 (important for catalytic activity)

Ligand- & substrate-binding residues (19): 218; 232; 232; 292; 319; 340; 366; 390; 398; 402; 46; 448 …

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 139 (showing top): VERHAAK_AML_WITH_NPM1_MUTATED_DN, LEE_NEURAL_CREST_STEM_CELL_DN, ENK_UV_RESPONSE_KERATINOCYTE_UP, GOBP_MONOSACCHARIDE_CATABOLIC_PROCESS, GOLDRATH_ANTIGEN_RESPONSE, ABE_VEGFA_TARGETS_2HR, GOBP_CARBOHYDRATE_METABOLIC_PROCESS, GOBP_PYRIMIDINE_CONTAINING_COMPOUND_METABOLIC_PROCESS, GNF2_CCNA1, KEGG_PENTOSE_PHOSPHATE_PATHWAY, GOBP_GLUCOSE_METABOLIC_PROCESS, HELLER_HDAC_TARGETS_SILENCED_BY_METHYLATION_UP, GOBP_SMALL_MOLECULE_CATABOLIC_PROCESS, GOBP_CARBOHYDRATE_CATABOLIC_PROCESS, GOBP_MONOSACCHARIDE_METABOLIC_PROCESS

GO Biological Process (2): glucose catabolic process (GO:0006007), thiamine metabolic process (GO:0006772)

GO Molecular Function (4): transketolase activity (GO:0004802), thiamine pyrophosphate binding (GO:0030976), metal ion binding (GO:0046872), transferase activity (GO:0016740)

GO Cellular Component (2): cytosol (GO:0005829), cytoplasm (GO:0005737)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cation binding	2
cellular anatomical structure	2
glucose metabolic process	1
hexose catabolic process	1
primary alcohol metabolic process	1
thiamine-containing compound metabolic process	1
transketolase or transaldolase activity	1
vitamin binding	1
anion binding	1
quaternary ammonium group binding	1
heterocyclic compound binding	1
sulfur compound binding	1
catalytic activity	1
cytoplasm	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

3251 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TKTL1	TALDO1	P37837	943
TKTL1	TPK1	Q9H3S4	943
TKTL1	TEX28	O15482	921
TKTL1	H6PD	O95479	846
TKTL1	PGD	P52209	833
TKTL1	G6PD	P11413	814
TKTL1	RPIA	P49247	799
TKTL1	RPE	Q96AT9	776
TKTL1	RPEL1	Q2QD12	764
TKTL1	TPI1	P00938	731
TKTL1	GAPDH	P00354	725
TKTL1	GPI	P06744	701
TKTL1	PGLS	O95336	661
TKTL1	PGK2	P07205	652
TKTL1	ENO1	P06733	640

IntAct

3 interactions, top by confidence:

A	B	Type	Score
TKTL1	DNAJB5	psi-mi:“MI:0914”(association)	0.530

BioGRID (17): HSP90AB4P (Affinity Capture-MS), DNAJB5 (Affinity Capture-MS), TUBB8 (Affinity Capture-MS), RICTOR (Affinity Capture-MS), VSIG8 (Affinity Capture-MS), TUBA1A (Affinity Capture-MS), HSP90AB4P (Affinity Capture-MS), VSIG8 (Affinity Capture-MS), DNAJB5 (Affinity Capture-MS), TUBB8 (Affinity Capture-MS), TKTL1 (Cross-Linking-MS (XL-MS)), TKTL1 (Cross-Linking-MS (XL-MS)), TKT (Cross-Linking-MS (XL-MS)), CUX2 (Cross-Linking-MS (XL-MS)), TKTL1 (Cross-Linking-MS (XL-MS))

ESM2 similar proteins: A5D6U8, A6NGU5, B5MD39, B8NM71, D4B387, O00754, O09159, O35409, P05187, P06865, P07314, P07686, P0DPU3, P0DPU6, P15693, P17439, P19111, P19440, P20060, P20735, P24822, P29416, P36268, P49614, P51740, P51854, P70627, Q0V8R6, Q14390, Q29451, Q29548, Q4R6M8, Q501L1, Q5RC84, Q5RFI5, Q5XIG6, Q60928, Q60HE9, Q641X3, Q680I5

Diamond homologs: A0AIG6, A1K4R0, A1W4U9, A2C220, A2C9X1, A4SDG1, A5D2Z6, A5N7J2, A6KXB3, A6VKQ3, A7Z6J5, A8FF11, A8FYL0, A9VGD1, B0C8J3, B0JL88, B0TEJ5, B1I3J6, B1WWM7, B1Z1G2, B2A526, B2J5P1, B2V4R3, B4RVY8, B7HB48, B7HNU0, B7IXG8, B7JM28, B7JVJ6, B7KAF7, B8D2I3, B8E247, B8FQ45, B8HWL8, B9E104, B9L1L6, B9MEU8, C0ZC10, C1L2S1, C3LJV1

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	71
Likely benign	4
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

1809 predictions. Top by Δscore:

Variant	Effect	Δscore
X:154295991:CGGGT:C	donor_loss	1.0000
X:154295992:GG:G	donor_gain	1.0000
X:154295993:GG:G	donor_gain	1.0000
X:154295993:GGTAA:G	donor_loss	1.0000
X:154295994:G:GG	donor_gain	1.0000
X:154295994:GTAAG:G	donor_loss	1.0000
X:154295995:T:G	donor_loss	1.0000
X:154305302:A:AG	acceptor_gain	1.0000
X:154305303:G:GG	acceptor_gain	1.0000
X:154305303:GC:G	acceptor_gain	1.0000
X:154305303:GCC:G	acceptor_gain	1.0000
X:154305303:GCCAC:G	acceptor_gain	1.0000
X:154305417:CAAAG:C	donor_loss	1.0000
X:154305418:AAAG:A	donor_loss	1.0000
X:154305419:AAGG:A	donor_loss	1.0000
X:154305422:G:A	donor_loss	1.0000
X:154305423:T:A	donor_loss	1.0000
X:154309340:TACA:T	acceptor_loss	1.0000
X:154309341:ACAG:A	acceptor_loss	1.0000
X:154309342:CA:C	acceptor_loss	1.0000
X:154309343:A:AC	acceptor_loss	1.0000
X:154309343:A:AG	acceptor_gain	1.0000
X:154309344:G:GA	acceptor_gain	1.0000
X:154309344:G:GT	acceptor_loss	1.0000
X:154309344:GA:G	acceptor_gain	1.0000
X:154309344:GAGA:G	acceptor_gain	1.0000
X:154310833:CAGCT:C	acceptor_loss	1.0000
X:154310834:A:AG	acceptor_gain	1.0000
X:154310834:A:AT	acceptor_loss	1.0000
X:154310835:G:GT	acceptor_gain	1.0000

AlphaMissense

3927 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
X:154311112:T:A	W182R	0.992
X:154311112:T:C	W182R	0.992
X:154323311:G:C	A431P	0.981
X:154327625:T:A	V479D	0.980
X:154329534:T:A	V546D	0.974
X:154311200:C:A	A211D	0.970
X:154311199:G:C	A211P	0.968
X:154320802:T:C	F359L	0.968
X:154320804:T:A	F359L	0.968
X:154320804:T:G	F359L	0.968
X:154310907:C:A	A141D	0.967
X:154310894:G:C	A137P	0.964
X:154310931:T:C	L149P	0.964
X:154323312:C:A	A431D	0.962
X:154310846:T:C	F121L	0.961
X:154310848:C:A	F121L	0.961
X:154310848:C:G	F121L	0.961
X:154327663:G:C	A492P	0.958
X:154323323:G:C	A435P	0.955
X:154309411:G:C	A107P	0.953
X:154311023:T:C	F180L	0.953
X:154311025:T:A	F180L	0.953
X:154311025:T:G	F180L	0.953
X:154323239:G:C	D407H	0.953
X:154327865:T:C	F509L	0.952
X:154327867:T:A	F509L	0.952
X:154327867:T:G	F509L	0.952
X:154320773:G:A	G349D	0.951
X:154329530:G:C	A545P	0.950
X:154311194:C:A	P209H	0.948

dbSNP variants (sampled 300 via entrez): RS1000108049 (X:154318041 G>A), RS1000412631 (X:154330230 C>G), RS1000441279 (X:154324021 G>A), RS1000574206 (X:154298060 T>G), RS1000728331 (X:154306159 A>T), RS1000803213 (X:154306574 C>G), RS1000955947 (X:154318857 A>G), RS1001043583 (X:154325203 C>T), RS1001155241 (X:154297886 G>A), RS1001251830 (X:154312886 C>A,G,T), RS1001582055 (X:154309884 A>C,G), RS1001619587 (X:154316440 C>G), RS1001718751 (X:154322908 A>G,T), RS1001878606 (X:154301205 T>C,G), RS1001885736 (X:154328994 T>C)

Disease associations

OMIM: gene MIM:300044 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

8 associations (top):

Study	Trait	p-value
GCST001873_1	Red blood cell traits	2.000000e-16
GCST001873_4	Red blood cell traits	4.000000e-18
GCST004713_12	Testicular germ cell tumor	4.000000e-08
GCST010002_98	Refractive error	1.000000e-08
GCST90002385_595	High light scatter reticulocyte count	3.000000e-28
GCST90002386_507	High light scatter reticulocyte percentage of red cells	5.000000e-26
GCST90002405_584	Reticulocyte count	1.000000e-21
GCST90002406_584	Reticulocyte fraction of red cells	1.000000e-19

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0004348	hematocrit
EFO:0004509	hemoglobin measurement
EFO:0007986	reticulocyte count

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

20 total (human), top 20 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, decreases expression, increases methylation, affects cotreatment, increases expression	6
trichostatin A	increases expression, affects cotreatment	3
sodium arsenite	increases expression	3
Decitabine	increases expression	2
2,4,5,2’,4’,5’-hexachlorobiphenyl	increases 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	affects cotreatment, increases expression	1
abrine	increases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
bisphenol S	decreases methylation	1
Panobinostat	increases expression, affects cotreatment	1
Acetaminophen	increases expression	1
Amiodarone	increases expression	1
Benzo(a)pyrene	affects methylation	1
Carbamazepine	affects expression	1
Folic Acid	decreases expression	1
Oxygen	affects reaction, increases expression	1
Gold Compounds	decreases expression	1
Acrylamide	decreases expression	1

Clinical trials (associated diseases)

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