TECR

Summary

TECR (trans-2,3-enoyl-CoA reductase, HGNC:4551) is a protein-coding gene on chromosome 19p13.12, encoding Very-long-chain enoyl-CoA reductase (Q9NZ01). Involved in both the production of very long-chain fatty acids for sphingolipid synthesis and the degradation of the sphingosine moiety in sphingolipids through the sphingosine 1-phosphate metabolic pathway. It is a selective cancer dependency (DepMap: 10.1% of cell lines).

This gene encodes a multi-pass membrane protein that resides in the endoplasmic reticulum, and belongs to the steroid 5-alpha reductase family. The elongation of microsomal long and very long chain fatty acid consists of 4 sequential reactions. This protein catalyzes the final step, reducing trans-2,3-enoyl-CoA to saturated acyl-CoA. Alternatively spliced transcript variants have been found for this gene.

Source: NCBI Gene 9524 — RefSeq curated summary.

At a glance

• Gene–disease (curated): autosomal recessive non-syndromic intellectual disability (Supportive, GenCC) — +2 more curated relationships
• GWAS associations: 1
• Clinical variants (ClinVar): 77 total
• Phenotypes (HPO): 6
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• Cancer dependency (DepMap): dependent in 10.1% of screened cell lines
• MANE Select transcript: NM_138501

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:4551
Approved symbol	TECR
Name	trans-2,3-enoyl-CoA reductase
Location	19p13.12
Locus type	gene with protein product
Status	Approved
Aliases	TER, MRT14
Ensembl gene	ENSG00000099797
Ensembl biotype	protein_coding
OMIM	610057
Entrez	9524

Gene structure

Transcript identifiers

Ensembl transcripts: 41 — 18 protein_coding, 15 retained_intron, 6 protein_coding_CDS_not_defined, 2 nonsense_mediated_decay

ENST00000215567, ENST00000593637, ENST00000593775, ENST00000594545, ENST00000594807, ENST00000594958, ENST00000596073, ENST00000596164, ENST00000596953, ENST00000597607, ENST00000598298, ENST00000598333, ENST00000598408, ENST00000598715, ENST00000598918, ENST00000598987, ENST00000599101, ENST00000599646, ENST00000600076, ENST00000600083, ENST00000600395, ENST00000601187, ENST00000601350, ENST00000601461, ENST00000601652, ENST00000642961, ENST00000882752, ENST00000882753, ENST00000882754, ENST00000882755, ENST00000882756, ENST00000882757, ENST00000882758, ENST00000913609, ENST00000913610, ENST00000913611, ENST00000913612, ENST00000971293, ENST00000971294, ENST00000971295, ENST00000971296

RefSeq mRNA: 2 — MANE Select: NM_138501 NM_001321170, NM_138501

CCDS: CCDS12313

Canonical transcript exons

ENST00000215567 — 13 exons

Exon	Start	End
ENSE00003116576	14529594	14529711
ENSE00003472442	14565618	14565663
ENSE00003476036	14564786	14564858
ENSE00003481743	14563982	14564097
ENSE00003505900	14564182	14564287
ENSE00003507354	14563206	14563257
ENSE00003537601	14562525	14562575
ENSE00003541664	14563658	14563702
ENSE00003587283	14565066	14565123
ENSE00003678996	14563800	14563903
ENSE00003691202	14565202	14565290
ENSE00003786664	14564949	14564992
ENSE00003850515	14565744	14565980

Expression profiles

Bgee: expression breadth ubiquitous, 195 present calls, max score 99.29.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 243.8196 / max 1884.0276, expressed in 1828 samples.

FANTOM5 promoters (10 alternative TSS)

Promoter ID	TPM avg	Samples expressed
174261	177.5435	1828
174262	59.7610	1816
174265	2.3431	504
208709	1.7156	879
174270	0.8919	159
174276	0.8676	485
174277	0.2717	124
174272	0.2308	80
174264	0.1198	49
208707	0.0747	40

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
lower esophagus mucosa	UBERON:0035834	99.29	gold quality
right hemisphere of cerebellum	UBERON:0014890	99.25	gold quality
left testis	UBERON:0004533	99.21	gold quality
right testis	UBERON:0004534	99.17	gold quality
skin of abdomen	UBERON:0001416	99.07	gold quality
cerebellar hemisphere	UBERON:0002245	99.03	gold quality
skin of leg	UBERON:0001511	99.01	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	99.00	gold quality
cerebellar cortex	UBERON:0002129	98.92	gold quality
minor salivary gland	UBERON:0001830	98.89	gold quality
hindlimb stylopod muscle	UBERON:0004252	98.83	gold quality
right adrenal gland cortex	UBERON:0035827	98.80	gold quality
right adrenal gland	UBERON:0001233	98.78	gold quality
right frontal lobe	UBERON:0002810	98.74	gold quality
left adrenal gland	UBERON:0001234	98.64	gold quality
left adrenal gland cortex	UBERON:0035825	98.63	gold quality
anterior cingulate cortex	UBERON:0009835	98.49	gold quality
gastrocnemius	UBERON:0001388	98.40	gold quality
mucosa of transverse colon	UBERON:0004991	98.35	gold quality
Brodmann (1909) area 9	UBERON:0013540	98.35	gold quality
right uterine tube	UBERON:0001302	98.34	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	98.24	gold quality
ectocervix	UBERON:0012249	98.13	gold quality
muscle of leg	UBERON:0001383	98.10	gold quality
endocervix	UBERON:0000458	97.84	gold quality
right lobe of thyroid gland	UBERON:0001119	97.72	gold quality
metanephros cortex	UBERON:0010533	97.64	gold quality
left lobe of thyroid gland	UBERON:0001120	97.58	gold quality
small intestine Peyer’s patch	UBERON:0003454	97.58	gold quality
right ovary	UBERON:0002118	97.54	gold quality

Single-cell (SCXA)

Detected in 5 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-HCAD-25	yes	4.21
E-MTAB-10596	no	675.15
E-MTAB-6524	no	134.47
E-CURD-120	no	6.14
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

4 targeting TECR, 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-361-3P	99.19	66.45	1381
HSA-MIR-423-5P	98.69	67.48	1522
HSA-MIR-3135B	98.61	65.33	1470
HSA-MIR-3184-5P	98.56	67.13	1491

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 10.1% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 5)

• Exome sequencing reveals a novel mutation for autosomal recessive non-syndromic mental retardation in the TECR gene on chromosome 19p13. (PMID:21212097)
• P182L mutation reduces the activity and stability of the TECR enzyme. (PMID:24220030)
• Data indicate that trans-2-enoyl-CoA reductase TER is involved in both very long-chain fatty acids (VLCFAs) synthesis and sphingosine degradation within sphingolipids. (PMID:25049234)
• Catalytic mechanism of trans-2-enoyl-CoA reductases in the fatty acid elongation cycle and its cooperative action with fatty acid elongases. (PMID:38224948)
• The 3-hydroxyacyl-CoA dehydratase 1/2 form complex with trans-2-enoyl-CoA reductase involved in substrates transfer in very long chain fatty acid elongation. (PMID:38422897)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	tecrb	ENSDARG00000025904
danio_rerio	tecra	ENSDARG00000101585
mus_musculus	Tecr	ENSMUSG00000031708
rattus_norvegicus	Tecrl2	ENSRNOG00000021808
drosophila_melanogaster	Sc2	FBGN0035471
caenorhabditis_elegans		WBGENE00000198

Paralogs (3): SRD5A1 (ENSG00000145545), TECRL (ENSG00000205678), SRD5A2 (ENSG00000277893)

Protein

Protein identifiers

Very-long-chain enoyl-CoA reductase — Q9NZ01 (reviewed: Q9NZ01)

Alternative names: Synaptic glycoprotein SC2, Trans-2,3-enoyl-CoA reductase

All UniProt accessions (5): Q9NZ01, M0R2E5, M0R2N5, M0R329, M0R3C3

UniProt curated annotations — full annotation on UniProt →

Function. Involved in both the production of very long-chain fatty acids for sphingolipid synthesis and the degradation of the sphingosine moiety in sphingolipids through the sphingosine 1-phosphate metabolic pathway. Catalyzes the last of the four reactions of the long-chain fatty acids elongation cycle. This endoplasmic reticulum-bound enzymatic process, allows the addition of 2 carbons to the chain of long- and very long-chain fatty acids/VLCFAs per cycle. This enzyme reduces the trans-2,3-enoyl-CoA fatty acid intermediate to an acyl-CoA that can be further elongated by entering a new cycle of elongation. Thereby, it participates in the production of VLCFAs of different chain lengths that are involved in multiple biological processes as precursors of membrane lipids and lipid mediators. Catalyzes the saturation step of the sphingosine 1-phosphate metabolic pathway, the conversion of trans-2-hexadecenoyl-CoA to palmitoyl-CoA.

Subunit / interactions. Interacts with ELOVL1 and LASS2. Interacts with HACD1 and HACD2 (via the third lumenal loop), but not with HACD3 and HACD4. Interacts with ELOVL1, ELOVL2, ELOVL3, ELOVL5 and ELOVL7 in the presence of acyl-CoA; interaction with HACD1/2 and that with ELOVLs are mutually exclusive.

Subcellular location. Endoplasmic reticulum membrane.

Tissue specificity. Expressed in most tissues tested. Highly expressed in skeletal muscle.

Post-translational modifications. Glycosylated.

Disease relevance. Intellectual developmental disorder, autosomal recessive 14 (MRT14) [MIM:614020] A disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. The disease is caused by variants affecting the gene represented in this entry.

Pathway. Lipid metabolism; fatty acid biosynthesis. Lipid metabolism; sphingolipid metabolism.

Similarity. Belongs to the steroid 5-alpha reductase family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9NZ01-1	1	yes
Q9NZ01-2	2

RefSeq proteins (2): NP_001308099, NP_612510* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001104	3-oxo-5_a-steroid_4-DH_C	Domain
IPR029071	Ubiquitin-like_domsf	Homologous_superfamily
IPR039357	SRD5A/TECR	Family
IPR049127	TECR-like_N	Domain

Pfam: PF02544, PF21696

Enzyme classification (BRENDA):

• EC 1.3.1.93 — very-long-chain enoyl-CoA reductase (BRENDA: 6 organisms, 3 substrates, 0 inhibitors, 0 Km, 0 kcat entries)

Catalyzed reactions (Rhea), 6 shown:

• a very-long-chain 2,3-saturated fatty acyl-CoA + NADP(+) = a very-long-chain (2E)-enoyl-CoA + NADPH + H(+) (RHEA:14473)
• octadecanoyl-CoA + NADP(+) = (2E)-octadecenoyl-CoA + NADPH + H(+) (RHEA:35351)
• (2E)-hexadecenoyl-CoA + NADPH + H(+) = hexadecanoyl-CoA + NADP(+) (RHEA:36143)
• (2E,8Z,11Z,14Z)-eicosatetraenoyl-CoA + NADPH + H(+) = (8Z,11Z,14Z)-eicosatrienoyl-CoA + NADP(+) (RHEA:39319)
• (2E,7Z,10Z,13Z,16Z)-docosapentaenoyl-CoA + NADPH + H(+) = (7Z,10Z,13Z,16Z)-docosatetraenoyl-CoA + NADP(+) (RHEA:39331)
• (2E,7Z,10Z,13Z,16Z,19Z)-docosahexaenoyl-CoA + NADPH + H(+) = (7Z,10Z,13Z,16Z,19Z)-docosapentaenoyl-CoA + NADP(+) (RHEA:39467)

UniProt features (29 total): topological domain 7, transmembrane region 6, strand 5, modified residue 3, sequence conflict 2, turn 2, chain 1, splice variant 1, sequence variant 1, helix 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
2DZJ	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9NZ01-F1	94.45	0.90

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 (3): 22, 58, 60

Function

Pathways and Gene Ontology

Reactome pathways

5 pathways

ID	Pathway
R-HSA-75876	Synthesis of very long-chain fatty acyl-CoAs
R-HSA-1430728	Metabolism
R-HSA-556833	Metabolism of lipids
R-HSA-75105	Fatty acyl-CoA biosynthesis
R-HSA-8978868	Fatty acid metabolism

MSigDB gene sets: 203 (showing top): REACTOME_SYNTHESIS_OF_VERY_LONG_CHAIN_FATTY_ACYL_COAS, TGCGCANK_UNKNOWN, GOMF_OXIDOREDUCTASE_ACTIVITY_ACTING_ON_THE_CH_CH_GROUP_OF_DONORS, ENK_UV_RESPONSE_KERATINOCYTE_UP, ACEVEDO_NORMAL_TISSUE_ADJACENT_TO_LIVER_TUMOR_DN, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, LUCAS_HNF4A_TARGETS_UP, GOBP_NUCLEOSIDE_PHOSPHATE_BIOSYNTHETIC_PROCESS, GHO_ATF5_TARGETS_DN, GOBP_MONOCARBOXYLIC_ACID_METABOLIC_PROCESS, KEGG_BIOSYNTHESIS_OF_UNSATURATED_FATTY_ACIDS, GOBP_ORGANOPHOSPHATE_BIOSYNTHETIC_PROCESS, GOBP_ORGANIC_ACID_BIOSYNTHETIC_PROCESS, GOBP_NUCLEOBASE_CONTAINING_SMALL_MOLECULE_METABOLIC_PROCESS, GOBP_SMALL_MOLECULE_BIOSYNTHETIC_PROCESS

GO Biological Process (7): sphingolipid metabolic process (GO:0006665), fatty acid elongation (GO:0030497), long-chain fatty-acyl-CoA biosynthetic process (GO:0035338), very long-chain fatty acid biosynthetic process (GO:0042761), lipid metabolic process (GO:0006629), fatty acid metabolic process (GO:0006631), fatty acid biosynthetic process (GO:0006633)

GO Molecular Function (5): very-long-chain fatty acyl-CoA dehydrogenase activity (GO:0017099), very-long-chain enoyl-CoA reductase activity (GO:0102758), protein binding (GO:0005515), oxidoreductase activity (GO:0016491), oxidoreductase activity, acting on the CH-CH group of donors (GO:0016627)

GO Cellular Component (4): nucleus (GO:0005634), endoplasmic reticulum (GO:0005783), endoplasmic reticulum membrane (GO:0005789), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-4 pathways:

Category	Pathways
Fatty acyl-CoA biosynthesis	1
Metabolism	1
Fatty acid metabolism	1
Metabolism of lipids	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
lipid metabolic process	2
fatty acid biosynthetic process	2
intracellular membrane-bounded organelle	2
long-chain fatty-acyl-CoA metabolic process	1
fatty-acyl-CoA biosynthetic process	1
very long-chain fatty acid metabolic process	1
primary metabolic process	1
monocarboxylic acid metabolic process	1
fatty acid metabolic process	1
lipid biosynthetic process	1
monocarboxylic acid biosynthetic process	1
acyl-CoA dehydrogenase activity	1
oxidoreductase activity, acting on the CH-CH group of donors, NAD or NADP as acceptor	1
binding	1
catalytic activity	1
oxidoreductase activity	1
cytoplasm	1
endomembrane system	1
organelle membrane	1
nuclear outer membrane-endoplasmic reticulum membrane network	1
endoplasmic reticulum subcompartment	1
cellular anatomical structure	1

Protein interactions and networks

STRING

1318 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TECR	ERMAP	Q96PL5	918
TECR	HSD17B12	Q53GQ0	902
TECR	PIK3C2B	O00750	894
TECR	DNAJB7	Q7Z6W7	882
TECR	SRD5A3	Q9H8P0	859
TECR	SCP2	P22307	765
TECR	ACAA1	P09110	749
TECR	ELOVL6	Q9H5J4	736
TECR	CA9	Q16790	697
TECR	HACD4	Q5VWC8	593
TECR	COASY	Q13057	590
TECR	HACD2	Q6Y1H2	588
TECR	CST11	Q9H112	582
TECR	HACD3	Q9P035	581
TECR	PAF1	Q8N7H5	571

IntAct

284 interactions, top by confidence:

A	B	Type	Score
MAP3K14	CHUK	psi-mi:“MI:0914”(association)	0.950
TECR	HACD2	psi-mi:“MI:0915”(physical association)	0.850
HACD2	TECR	psi-mi:“MI:0915”(physical association)	0.850
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
HACD1	TECR	psi-mi:“MI:0915”(physical association)	0.700
TECR	ELOVL4	psi-mi:“MI:0915”(physical association)	0.670
ELOVL4	TECR	psi-mi:“MI:0915”(physical association)	0.670
CANX	PGRMC1	psi-mi:“MI:0914”(association)	0.570
TECR	SLC7A14	psi-mi:“MI:0915”(physical association)	0.560
TECR	STING1	psi-mi:“MI:0915”(physical association)	0.560
CREB3L1	TECR	psi-mi:“MI:0915”(physical association)	0.560
CRB3	TECR	psi-mi:“MI:0915”(physical association)	0.560
TECR	ERGIC3	psi-mi:“MI:0915”(physical association)	0.560
STOM	TECR	psi-mi:“MI:0915”(physical association)	0.560
JAGN1	TECR	psi-mi:“MI:0915”(physical association)	0.560
CD79A	TECR	psi-mi:“MI:0915”(physical association)	0.560
MUC1	TECR	psi-mi:“MI:0915”(physical association)	0.560
ARL13B	TECR	psi-mi:“MI:0915”(physical association)	0.560
GET1	TECR	psi-mi:“MI:0915”(physical association)	0.560
SLC7A14	TECR	psi-mi:“MI:0915”(physical association)	0.560
RETREG3	TECR	psi-mi:“MI:0915”(physical association)	0.560
PGRMC2	TECR	psi-mi:“MI:0915”(physical association)	0.560
FAM209A	TECR	psi-mi:“MI:0915”(physical association)	0.560
MFSD14B	TECR	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (375): PTPLB (Two-hybrid), TECR (Affinity Capture-MS), TECR (Affinity Capture-MS), TECR (Affinity Capture-MS), TECR (Affinity Capture-MS), TECR (Affinity Capture-MS), TECR (Affinity Capture-MS), ACADM (Co-fractionation), ATP5C1 (Co-fractionation), CANX (Co-fractionation), CCT6A (Co-fractionation), CISD1 (Co-fractionation), CLTC (Co-fractionation), DDOST (Co-fractionation), DDX39B (Co-fractionation)

ESM2 similar proteins: A2AKQ0, A2VE55, A5GFZ5, B8B7Q4, F4JN00, O14494, O42602, O60762, O70152, O75352, O88956, P0CK96, P60588, Q15B89, Q1JQ93, Q28HF8, Q2M3R5, Q3ZCD7, Q4L208, Q4R8V4, Q52KD1, Q5PT50, Q5PT53, Q5RDC9, Q5XF09, Q5ZJ75, Q5ZJH8, Q64232, Q6DBP3, Q6DHK8, Q6NMB6, Q6ZL17, Q762D5, Q76EJ3, Q7T0V6, Q8C811, Q8GUJ1, Q8IVW8, Q8R4D1, Q8RXL8

Diamond homologs: A2XWN6, A5PJS2, B8B6G5, I1HTF7, O18765, O94511, P18405, P31213, P31214, Q28891, Q28892, Q2QDF6, Q38944, Q3SZ89, Q3ZCD7, Q55C17, Q57ZC7, Q5K2N1, Q64232, Q68FF9, Q7F0Q2, Q7XUH5, Q8AVI9, Q99190, Q99N99, Q9CY27, Q9M2U2, Q9N5Y2, Q9NZ01, Q9VLP9, C7T2J9, D2HBV9, P24008, Q17428, Q5RJM1, Q9H8P0, Q9SI62, Q9WUP4, Q5HYJ1, Q9CAH5

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 153 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
NIK–>noncanonical NF-kB signaling	5	10.8×	8e-03
Defective CFTR causes cystic fibrosis	5	10.4×	8e-03
RHOQ GTPase cycle	6	10.3×	3e-03
Dectin-1 mediated noncanonical NF-kB signaling	5	10.2×	8e-03
RHOJ GTPase cycle	5	9.4×	1e-02
Activation of NF-kappaB in B cells	5	9.3×	1e-02
Constitutive Signaling by Aberrant PI3K in Cancer	7	8.4×	3e-03
MAPK6/MAPK4 signaling	6	7.7×	8e-03

GO biological processes:

GO term	Partners	Fold	FDR
cell surface receptor protein tyrosine kinase signaling pathway	9	12.5×	5e-05
positive regulation of neuron projection development	7	7.7×	9e-03
endoplasmic reticulum to Golgi vesicle-mediated transport	7	7.6×	9e-03
positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction	10	6.3×	3e-03
protein phosphorylation	10	5.4×	6e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	35
Likely benign	15
Benign	6

Top pathogenic / likely-pathogenic (0)

SpliceAI

2153 predictions. Top by Δscore:

Variant	Effect	Δscore
19:14518134:CACA:C	donor_loss	1.0000
19:14518135:ACAC:A	donor_loss	1.0000
19:14518138:C:A	donor_loss	1.0000
19:14518141:T:TA	donor_gain	1.0000
19:14529710:AGGT:A	donor_loss	1.0000
19:14529711:GGTA:G	donor_loss	1.0000
19:14529712:GTAAG:G	donor_loss	1.0000
19:14529713:T:G	donor_loss	1.0000
19:14562521:C:CA	acceptor_gain	1.0000
19:14562574:AGGT:A	donor_loss	1.0000
19:14562575:GGTAG:G	donor_loss	1.0000
19:14562576:G:GA	donor_loss	1.0000
19:14562577:T:G	donor_loss	1.0000
19:14563202:CCAGG:C	acceptor_loss	1.0000
19:14563204:A:G	acceptor_loss	1.0000
19:14563205:G:A	acceptor_loss	1.0000
19:14563253:GACCC:G	donor_gain	1.0000
19:14563254:ACCC:A	donor_gain	1.0000
19:14563255:CCC:C	donor_gain	1.0000
19:14563256:CC:C	donor_gain	1.0000
19:14563256:CCGT:C	donor_loss	1.0000
19:14563257:CG:C	donor_loss	1.0000
19:14563258:G:GG	donor_gain	1.0000
19:14563656:A:AG	acceptor_gain	1.0000
19:14563657:G:GA	acceptor_gain	1.0000
19:14563700:CCAGT:C	donor_loss	1.0000
19:14563702:AGT:A	donor_loss	1.0000
19:14563703:G:GG	donor_gain	1.0000
19:14563703:GT:G	donor_loss	1.0000
19:14563795:TGCA:T	acceptor_loss	1.0000

AlphaMissense

2010 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:14563880:G:T	G82W	1.000
19:14563895:T:A	W87R	1.000
19:14563895:T:C	W87R	1.000
19:14563897:G:C	W87C	1.000
19:14563897:G:T	W87C	1.000
19:14563983:T:A	V90D	1.000
19:14563985:T:A	F91I	1.000
19:14563985:T:C	F91L	1.000
19:14563986:T:C	F91S	1.000
19:14563986:T:G	F91C	1.000
19:14563987:C:A	F91L	1.000
19:14563987:C:G	F91L	1.000
19:14563996:G:C	E94D	1.000
19:14563996:G:T	E94D	1.000
19:14563997:T:C	Y95H	1.000
19:14564003:G:A	G97R	1.000
19:14564003:G:C	G97R	1.000
19:14564004:G:A	G97E	1.000
19:14564207:C:G	H137D	1.000
19:14564218:G:C	K140N	1.000
19:14564218:G:T	K140N	1.000
19:14564219:C:A	R141S	1.000
19:14564229:A:T	E144V	1.000
19:14564230:G:C	E144D	1.000
19:14564230:G:T	E144D	1.000
19:14564243:C:A	H149N	1.000
19:14564243:C:G	H149D	1.000
19:14564245:C:A	H149Q	1.000
19:14564245:C:G	H149Q	1.000
19:14564249:T:C	F151L	1.000

dbSNP variants (sampled 300 via entrez): RS1000000469 (19:14538647 C>T), RS1000267498 (19:14563165 T>TCC), RS1000378030 (19:14543847 T>G), RS1000579116 (19:14555127 T>G), RS1000646195 (19:14548886 C>T), RS1000700558 (19:14529351 G>A), RS1000770669 (19:14553434 T>C), RS1000816249 (19:14534415 T>G), RS1000823536 (19:14553676 A>C), RS1000881421 (19:14526977 G>C), RS1000893626 (19:14549977 GC>G), RS1000956889 (19:14558280 G>A), RS1000997449 (19:14548724 C>T), RS1001002959 (19:14532410 G>A,T), RS1001074799 (19:14558424 C>T)

Disease associations

OMIM: gene MIM:610057 | disease phenotypes: MIM:614020

GenCC curated gene-disease

Disease	Classification	Inheritance
autosomal recessive non-syndromic intellectual disability	Supportive	Autosomal recessive
intellectual disability, autosomal recessive 14	Limited	Autosomal recessive

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
intellectual disability	Limited	AR

Mondo (2): intellectual disability, autosomal recessive 14 (MONDO:0013528), autosomal recessive non-syndromic intellectual disability (MONDO:0019502)

Orphanet (1): Autosomal recessive non-syndromic intellectual disability (Orphanet:88616)

HPO phenotypes

6 total (6 of 6 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000189	Narrow palate
HP:0000750	Delayed speech and language development
HP:0001249	Intellectual disability
HP:0002080	Intention tremor
HP:0003593	Infantile onset

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST012490_63	Femur bone mineral density x serum urate levels interaction	4.000000e-11

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004531	urate measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5725074 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

1 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 1,538 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL1232461	MOLIBRESIB	2	1,538

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

ChEMBL bioactivities

5 potent at pChembl≥5 of 5 total, top 5 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
6.43	IC50	370	nM	MOLIBRESIB
5.88	Kd	1308	nM	CHEMBL5653589
5.88	ED50	1308	nM	CHEMBL5653589
5.41	Kd	3863	nM	CHEMBL3752910
5.41	ED50	3863	nM	CHEMBL3752910

PubChem BioAssay actives

3 with measured affinity, of 10 total; 3 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
2-[(4S)-6-(4-chlorophenyl)-8-methoxy-1-methyl-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepin-4-yl]-N-ethylacetamide	2179045: Inhibition of GPSN2 (unknown origin) incubated for 1 hr by colloidal coomassie staining based LC-MS/MS analysis	ic50	0.3700	uM
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149568: Binding affinity to human TECR incubated for 45 mins by Kinobead based pull down assay	kd	1.3078	uM
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149568: Binding affinity to human TECR incubated for 45 mins by Kinobead based pull down assay	kd	3.8632	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Air Pollutants	affects expression, increases abundance, decreases expression, increases expression	3
Valproic Acid	increases expression, increases methylation	2
bisphenol F	increases expression	1
bisphenol A	affects expression	1
sodium arsenate	decreases expression	1
beta-lapachone	decreases expression	1
cobaltous chloride	decreases expression	1
2-bromopalmitate	increases abundance, increases palmitoylation, decreases reaction	1
perfluorooctanoic acid	decreases expression	1
2,3-bis(3’-hydroxybenzyl)butyrolactone	affects cotreatment, increases expression	1
beta-methylcholine	affects expression	1
CGP 52608	affects binding, increases reaction	1
perfluoro-n-nonanoic acid	decreases expression	1
K 7174	decreases expression	1
GW 4064	affects cotreatment, decreases expression	1
obeticholic acid	decreases expression	1
erucylphospho-N,N,N-trimethylpropylammonium	decreases expression	1
bisphenol B	increases expression	1
bisphenol AF	increases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	decreases expression	1
Temozolomide	decreases expression	1
Sunitinib	increases expression	1
Arsenic Trioxide	increases expression	1
Air Pollutants, Occupational	affects expression	1
Arsenic	affects methylation	1
Atrazine	increases expression	1
Benzene	increases expression	1
Cadmium	decreases reaction, increases abundance, increases palmitoylation	1
Coumestrol	affects cotreatment, increases expression	1
Diazinon	increases methylation	1

ChEMBL screening assays

7 unique, capped per target: 7 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5652610	Binding	Binding affinity to human TECR incubated for 45 mins by Kinobead based pull down assay	NVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family. — ChemMedChem

Cellosaurus cell lines

1 cell lines: 1 transformed cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_B3J6	Abcam HEK293T TECR KO	Transformed cell line	Female

Clinical trials (associated diseases)

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