SECISBP2

Summary

SECISBP2 (SECIS binding protein 2, HGNC:30972) is a protein-coding gene on chromosome 9q22.2, encoding Selenocysteine insertion sequence-binding protein 2 (Q96T21). mRNA-binding protein that binds to the SECIS (selenocysteine insertion sequence) element present in the 3’-UTR of mRNAs encoding selenoproteins and facilitates the incorporation of the rare amino acid selenocysteine.

The protein encoded by this gene is one of the essential components of the machinery involved in co-translational insertion of selenocysteine (Sec) into selenoproteins. Sec is encoded by the UGA codon, which normally signals translation termination. The recoding of UGA as Sec codon requires a Sec insertion sequence (SECIS) element; present in the 3’ untranslated regions of eukaryotic selenoprotein mRNAs. This protein specifically binds to the SECIS element, which is stimulated by a Sec-specific translation elongation factor. Mutations in this gene have been associated with reduction in enzymatic activity of type II iodothyronine deiodinase (a selenoprotein) and abnormal thyroid hormone metabolism. Alternatively spliced transcript variants have been found for this gene.

Source: NCBI Gene 79048 — RefSeq curated summary.

At a glance

• Gene–disease (curated): thyroid hormone metabolism, abnormal 1 (Strong, GenCC) — +1 more curated relationship
• GWAS associations: 1
• Clinical variants (ClinVar): 181 total — 7 pathogenic, 6 likely-pathogenic
• Phenotypes (HPO): 22
• MANE Select transcript: NM_024077

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:30972
Approved symbol	SECISBP2
Name	SECIS binding protein 2
Location	9q22.2
Locus type	gene with protein product
Status	Approved
Aliases	SBP2
Ensembl gene	ENSG00000187742
Ensembl biotype	protein_coding
OMIM	607693
Entrez	79048

Gene structure

Transcript identifiers

Ensembl transcripts: 22 — 18 protein_coding, 4 protein_coding_CDS_not_defined

ENST00000339901, ENST00000375807, ENST00000425851, ENST00000440898, ENST00000470305, ENST00000477484, ENST00000496597, ENST00000498819, ENST00000534113, ENST00000858958, ENST00000858959, ENST00000858960, ENST00000858961, ENST00000935999, ENST00000936000, ENST00000936001, ENST00000936002, ENST00000936003, ENST00000936004, ENST00000960321, ENST00000960322, ENST00000960323

RefSeq mRNA: 8 — MANE Select: NM_024077 NM_001282688, NM_001282689, NM_001282690, NM_001354696, NM_001354697, NM_001354698, NM_001354702, NM_024077

CCDS: CCDS65076, CCDS65077, CCDS6683

Canonical transcript exons

ENST00000375807 — 17 exons

Exon	Start	End
ENSE00001291878	89328660	89328886
ENSE00001309134	89339864	89339953
ENSE00001317765	89332908	89332986
ENSE00001597774	89357999	89358191
ENSE00001600699	89348079	89348214
ENSE00001732656	89357411	89357565
ENSE00001794941	89346882	89347048
ENSE00001901994	89318500	89318612
ENSE00003516727	89338458	89338580
ENSE00003533125	89334522	89334730
ENSE00003543962	89349776	89349929
ENSE00003567868	89319652	89319797
ENSE00003571868	89350632	89350852
ENSE00003622529	89325897	89326038
ENSE00003689275	89325427	89325676
ENSE00003733573	89358721	89359663
ENSE00003784041	89341347	89341479

Expression profiles

Bgee: expression breadth ubiquitous, 280 present calls, max score 97.91.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 40.8491 / max 467.5189, expressed in 1818 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
97285	37.1590	1817
97284	2.8759	1386
97286	0.4652	236
97287	0.3490	176

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
secondary oocyte	CL:0000655	97.91	gold quality
sperm	CL:0000019	96.98	gold quality
oocyte	CL:0000023	96.77	gold quality
body of pancreas	UBERON:0001150	96.51	gold quality
left ovary	UBERON:0002119	96.46	gold quality
right uterine tube	UBERON:0001302	96.36	gold quality
right ovary	UBERON:0002118	95.87	gold quality
left testis	UBERON:0004533	95.53	gold quality
right testis	UBERON:0004534	95.50	gold quality
sural nerve	UBERON:0015488	95.44	gold quality
male germ cell	CL:0000015	95.43	gold quality
body of uterus	UBERON:0009853	95.42	gold quality
ganglionic eminence	UBERON:0004023	95.41	gold quality
left lobe of thyroid gland	UBERON:0001120	94.99	gold quality
right lung	UBERON:0002167	94.94	gold quality
calcaneal tendon	UBERON:0003701	94.92	gold quality
right lobe of thyroid gland	UBERON:0001119	94.86	gold quality
tibial nerve	UBERON:0001323	94.86	gold quality
adult organism	UBERON:0007023	94.76	gold quality
corpus epididymis	UBERON:0004359	94.75	gold quality
left uterine tube	UBERON:0001303	94.73	gold quality
testis	UBERON:0000473	94.71	gold quality
small intestine Peyer’s patch	UBERON:0003454	94.62	gold quality
endocervix	UBERON:0000458	94.61	gold quality
ovary	UBERON:0000992	94.55	gold quality
thyroid gland	UBERON:0002046	94.43	gold quality
cortical plate	UBERON:0005343	94.42	gold quality
adrenal tissue	UBERON:0018303	94.41	gold quality
mucosa of stomach	UBERON:0001199	94.40	gold quality
ectocervix	UBERON:0012249	94.05	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	13.72

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): DLX4

miRNA regulators (miRDB)

34 targeting SECISBP2, 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-513A-5P	100.00	69.77	2465
HSA-MIR-4760-3P	99.93	70.50	2385
HSA-MIR-3119	99.92	71.34	2390
HSA-MIR-12119	99.87	68.35	1653
HSA-MIR-544A	99.84	68.66	1965
HSA-MIR-3180-5P	99.82	69.12	2422
HSA-MIR-6844	99.82	70.69	2423
HSA-MIR-4668-5P	99.79	70.58	3782
HSA-MIR-4517	99.76	69.19	1867
HSA-MIR-4719	99.73	72.10	3329
HSA-MIR-4530	99.69	66.47	1509
HSA-MIR-7161-5P	99.68	68.92	1592
HSA-MIR-6887-3P	99.66	67.83	1778
HSA-MIR-1303	99.65	69.77	1662
HSA-MIR-548U	99.65	67.78	1463
HSA-MIR-4499	99.62	67.29	1470
HSA-MIR-497-3P	99.61	69.71	1990
HSA-MIR-24-3P	99.59	69.97	1934
HSA-MIR-4524A-5P	99.57	71.73	1193
HSA-MIR-4524B-5P	99.57	71.68	1195
HSA-MIR-4649-3P	99.56	66.90	1783
HSA-MIR-5584-5P	99.49	68.22	2814
HSA-MIR-6853-3P	99.36	70.79	1558
HSA-MIR-4687-5P	99.14	66.26	488
HSA-MIR-421	98.90	67.04	1883
HSA-MIR-935	98.82	69.36	1072
HSA-MIR-648	98.64	66.13	553
HSA-MIR-4733-3P	98.35	65.20	994
HSA-MIR-630	97.50	66.38	921
HSA-MIR-2467-5P	97.36	67.71	991

Literature-anchored findings (GeneRIF, showing 21)

• In addition to identifying key amino acids for SECIS recognition by SBP2, our findings led to the proposal that some of the recognition principles governing the 15.5 kD-U4 snRNA interaction must be similar in the SBP2-SECIS RNA complex (PMID:12403468)
• Oxidative stress induces nuclear accumulation of SBP2 via oxidation of cysteine residues within a redox-sensitive cysteine-rich domain. (PMID:16782878)
• Data suggest that SBP2 is a major determinant in dictating the hierarchy of selenoprotein synthesis via differential selenoprotein mRNA translation and sensitivity to nonsense-mediated decay. (PMID:17846120)
• SECIS binding induces a conformational change in SBP2 that recruits eEFSec, which in concert with the Sec incorporation domain gains access to the ribosomal A site (PMID:18948268)
• A report of a complex splicing pattern in the 5’-region of human SECISBP2, wherein at least eight splice variants encode five isoforms with varying N-terminal sequence. (PMID:19004874)
• CUG-BP1 and HuR act as factors that bind to the SBP2 3’ UTR, which suggests that TTR-RBPs play a role in the regulation of SBP2 (PMID:19106619)
• Seleniuim is obviously not a limiting factor in the SBP2 deficient individuals when regular daily selenium intake is provided (PMID:19265499)
• ca. 70% of the SBP2 sequence is disordered, whereas the RNA binding domain appears to be folded and functional. (PMID:19467292)
• SBP2 gene mutation producing early arrest in synthesis of full-length molecule. Demonstration that SBP2 isoforms containing all functional domains could be synthesized from three downstream ATGs explains the relatively mild phenotype caused by this defect (PMID:19602558)
• Results demonstrate that SECIS-binding protein 2 is required for protection against reactive oxygen species-induced cellular damage and cell survival. (PMID:19803747)
• Describe subjects with compound heterozygous defects in the SECISBP2 gene. These individuals have reduced synthesis of most of the 25 known human selenoproteins, resulting in a complex phenotype. (PMID:21084748)
• The patient showed typical symptoms of SBP2 deficiency, and novel compound heterozygous mutations were identified in SBP2 (p.M515fsX563/p.Q79X). (PMID:22247018)
• Selenocysteine insertion sequence (SECIS)-binding protein 2 alters conformational dynamics of residues involved in tRNA accommodation in 80 S ribosomes. (PMID:22308032)
• SBP2 makes direct contacts with a discrete region of the human 28S rRNA. (PMID:24850884)
• SBP2 interacts directly with four proteins of the SMN complex and the methylosome core proteins. (PMID:28115638)
• functions as a vital factor in selenoprotein translation and regulates the pro-oxidant/antioxidant balance in trophoblasts (PMID:28623977)
• Selenium-sensitive miR-181a-5p to participate and regulate SBP2 at post-transcriptional level. (PMID:30247797)
• In osteoarthritis pro-inflammatory factors mediate miR-181a-5p expression, and then miR-181a-5p regulates the pivotal selenoproteins GPX1 and GPX4 through its target SBP2, resulting in alterations to the overall activity of GPXs, which are the most important oxidation resistance proteins in cartilage. (PMID:30286747)
• SECISBP2 expression in healthy human palatal mucosa is strongly negatively correlated with serum cotinine levels. (PMID:31682009)
• SECISBP2 is a novel prognostic predictor that regulates selenoproteins in diffuse large B-cell lymphoma. (PMID:33077808)
• Human Genetic Disorders Resulting in Systemic Selenoprotein Deficiency. (PMID:34884733)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	secisbp2	ENSDARG00000073892
mus_musculus	Secisbp2	ENSMUSG00000035139
rattus_norvegicus	Secisbp2	ENSRNOG00000013773
drosophila_melanogaster	Sbp2	FBGN0087039

Paralogs (1): SECISBP2L (ENSG00000138593)

Protein

Protein identifiers

Selenocysteine insertion sequence-binding protein 2 — Q96T21 (reviewed: Q96T21)

All UniProt accessions (4): A0A1S5UZH3, Q96T21, Q4V370, Q5HYY5

UniProt curated annotations — full annotation on UniProt →

Function. mRNA-binding protein that binds to the SECIS (selenocysteine insertion sequence) element present in the 3’-UTR of mRNAs encoding selenoproteins and facilitates the incorporation of the rare amino acid selenocysteine. Insertion of selenocysteine at UGA codons is mediated by SECISBP2 and EEFSEC: SECISBP2 (1) specifically binds the SECIS sequence once the 80S ribosome encounters an in-frame UGA codon and (2) contacts the RPS27A/eS31 of the 40S ribosome before ribosome stalling. (3) GTP-bound EEFSEC then delivers selenocysteinyl-tRNA(Sec) to the 80S ribosome and adopts a preaccommodated state conformation. (4) After GTP hydrolysis, EEFSEC dissociates from the assembly, selenocysteinyl-tRNA(Sec) accommodates, and peptide bond synthesis and selenoprotein elongation occur.

Subcellular location. Nucleus Mitochondrion.

Tissue specificity. Expressed at high levels in testis.

Disease relevance. Thyroid hormone metabolism, abnormal, 1 (THMA1) [MIM:609698] A disorder associated with a reduction in type II iodothyronine deiodinase activity. The disease is caused by variants affecting the gene represented in this entry.

Miscellaneous. Contains a transit peptide at positions 1-15.

Isoforms (3)

UniProt ID	Names	Canonical?
Q96T21-1	1	yes
Q96T21-2	2, mtSBP2
Q96T21-3	3, SBP2_delta2

RefSeq proteins (8): NP_001269617, NP_001269618, NP_001269619, NP_001341625, NP_001341626, NP_001341627, NP_001341631, NP_076982* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR004038	Ribosomal_eL8/eL30/eS12/Gad45	Domain
IPR029064	Ribosomal_eL30-like_sf	Homologous_superfamily
IPR040051	SECISBP2	Family

Pfam: PF01248

UniProt features (22 total): compositionally biased region 7, region of interest 6, splice variant 3, sequence variant 2, sequence conflict 2, chain 1, short sequence motif 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
7ZJW	ELECTRON MICROSCOPY	2.8
7ZJX	ELECTRON MICROSCOPY	3.1

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96T21-F1	55.54	0.19

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-2408557	Selenocysteine synthesis
R-HSA-1430728	Metabolism
R-HSA-2408522	Selenoamino acid metabolism
R-HSA-71291	Metabolism of amino acids and derivatives

MSigDB gene sets: 198 (showing top): GOBP_REGULATION_OF_MRNA_CATABOLIC_PROCESS, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, AREB6_01, GOBP_NEUROGENESIS, BILD_SRC_ONCOGENIC_SIGNATURE, GOBP_FOREBRAIN_DEVELOPMENT, GOBP_TRANSLATION, GOBP_POST_TRANSCRIPTIONAL_REGULATION_OF_GENE_EXPRESSION, GOBP_REGULATION_OF_CATABOLIC_PROCESS, HFH1_01, GOBP_HEAD_DEVELOPMENT, GOBP_TRANSLATIONAL_ELONGATION, AACTTT_UNKNOWN, MYB_Q3, chr9q22

GO Biological Process (7): selenocysteine incorporation (GO:0001514), RNA catabolic process (GO:0006401), striatum development (GO:0021756), forebrain neuron development (GO:0021884), mRNA stabilization (GO:0048255), negative regulation of nuclear-transcribed mRNA catabolic process, nonsense-mediated decay (GO:2000623), translation (GO:0006412)

GO Molecular Function (6): DNA binding (GO:0003677), RNA binding (GO:0003723), mRNA 3’-UTR binding (GO:0003730), selenocysteine insertion sequence binding (GO:0035368), ribonucleoprotein complex binding (GO:0043021), protein binding (GO:0005515)

GO Cellular Component (4): nucleoplasm (GO:0005654), mitochondrion (GO:0005739), ribonucleoprotein complex (GO:1990904), nucleus (GO:0005634)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Selenoamino acid metabolism	1
Metabolism of amino acids and derivatives	1
Metabolism	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
negative regulation of mRNA catabolic process	2
nucleic acid binding	2
mRNA binding	2
intracellular membrane-bounded organelle	2
translational readthrough	1
RNA metabolic process	1
nucleic acid catabolic process	1
subpallium development	1
anatomical structure development	1
forebrain neuron differentiation	1
central nervous system neuron development	1
regulation of mRNA stability	1
RNA stabilization	1
nuclear-transcribed mRNA catabolic process, nonsense-mediated decay	1
regulation of nuclear-transcribed mRNA catabolic process, nonsense-mediated decay	1
peptidyltransferase activity	1
translational initiation	1
translational elongation	1
translational termination	1
macromolecule biosynthetic process	1
protein metabolic process	1
protein biosynthetic process	1
protein-containing complex binding	1
binding	1
nuclear lumen	1
cellular anatomical structure	1
cytoplasm	1
protein-containing complex	1

Protein interactions and networks

STRING

1962 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SECISBP2	EEFSEC	P57772	998
SECISBP2	DIO2	Q92813	916
SECISBP2	SELENOK	Q9Y6D0	900
SECISBP2	PSTK	Q8IV42	886
SECISBP2	TRNAU1AP	Q9NX07	881
SECISBP2	SELENOT	P62341	869
SECISBP2	SEPSECS	Q9HD40	867
SECISBP2	SELENON	Q9NZV5	861
SECISBP2	SELENOP	P49908	828
SECISBP2	GPX4	P36969	816
SECISBP2	SELENOF	O60613	810
SECISBP2	SELENOS	Q9BQE4	791
SECISBP2	SELENOW	P63302	787
SECISBP2	SEPHS2	Q99611	787
SECISBP2	SELENOO	Q9BVL4	769

IntAct

35 interactions, top by confidence:

A	B	Type	Score
SECISBP2	GOLGA2	psi-mi:“MI:0915”(physical association)	0.560
GOLGA2	SECISBP2	psi-mi:“MI:0915”(physical association)	0.560
FAM168A	SECISBP2	psi-mi:“MI:0915”(physical association)	0.560
HTT	SECISBP2	psi-mi:“MI:0915”(physical association)	0.560
SECISBP2	CCT6A	psi-mi:“MI:0915”(physical association)	0.400
SECISBP2	H2AC12	psi-mi:“MI:0915”(physical association)	0.400
SECISBP2	MYO18A	psi-mi:“MI:0915”(physical association)	0.400
PA	SECISBP2	psi-mi:“MI:0915”(physical association)	0.370
SECISBP2	SMAD9	psi-mi:“MI:0915”(physical association)	0.370
	SECISBP2	psi-mi:“MI:0915”(physical association)	0.370
EGLN3	FAM168B	psi-mi:“MI:0914”(association)	0.350
Prdm16	ESYT2	psi-mi:“MI:0914”(association)	0.350
PIP	RBM47	psi-mi:“MI:0914”(association)	0.350
KCNE3	PIK3R2	psi-mi:“MI:0914”(association)	0.350
TNFRSF1B	MAP3K7	psi-mi:“MI:0914”(association)	0.350
	NFIB	psi-mi:“MI:0914”(association)	0.350
PCM1	CCDC66	psi-mi:“MI:2364”(proximity)	0.270
SPICE1	CCDC66	psi-mi:“MI:2364”(proximity)	0.270
AGGF1	BLTP3B	psi-mi:“MI:2364”(proximity)	0.270
DGCR8	VWA8	psi-mi:“MI:2364”(proximity)	0.270
FXR2	RPSA2	psi-mi:“MI:2364”(proximity)	0.270
LARP4	CNOT1	psi-mi:“MI:2364”(proximity)	0.270
LIN28B	MEX3A	psi-mi:“MI:2364”(proximity)	0.270
RPS3	ESYT2	psi-mi:“MI:2364”(proximity)	0.270
UTP3	NACA	psi-mi:“MI:2364”(proximity)	0.270
ZC3H11A	ESYT2	psi-mi:“MI:2364”(proximity)	0.270
DDX6	RPSA2	psi-mi:“MI:2364”(proximity)	0.270

BioGRID (99): SECISBP2 (Two-hybrid), SECISBP2 (Reconstituted Complex), SECISBP2 (Proximity Label-MS), SECISBP2 (Proximity Label-MS), SECISBP2 (Affinity Capture-RNA), SECISBP2 (Affinity Capture-MS), SECISBP2 (Affinity Capture-MS), SECISBP2 (Two-hybrid), SECISBP2 (Proximity Label-MS), SECISBP2 (Proximity Label-MS), SECISBP2 (Proximity Label-MS), SECISBP2 (Proximity Label-MS), SECISBP2 (Proximity Label-MS), SECISBP2 (Proximity Label-MS), SECISBP2 (Proximity Label-MS)

ESM2 similar proteins: A0A1D5NVS8, A0AVK6, A2A891, A5GFT6, A5PLL1, A5X7A0, A7XYH5, A7XYJ6, B7ZS37, D3ZGB1, D4A4D7, D4A666, E1B7L7, E1BE02, E1BKK0, E1BLP6, E7F888, F1LMN3, F1QZ88, F6YVB9, F7EA39, O35914, O54916, P0C6C1, Q01804, Q14B70, Q3U1C4, Q3UUF8, Q566I1, Q58FA4, Q5RIX9, Q5ZJ69, Q68FE9, Q69ZF8, Q6A098, Q6S7F2, Q6ZSZ6, Q6ZU65, Q76L83, Q80WC1

Diamond homologs: Q3U1C4, Q6A098, Q93073, Q96T21, Q9QX72

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	7
Likely pathogenic	6
Uncertain significance	118
Likely benign	19
Benign	7

Top pathogenic / likely-pathogenic (13)

Variant ID	HGVS	Classification
1323572	NM_024077.5(SECISBP2):c.358C>T (p.Arg120Ter)	Pathogenic
1703052	NM_024077.5(SECISBP2):c.2308C>T (p.Arg770Ter)	Pathogenic
2581403	NM_024077.5(SECISBP2):c.1156_1159del (p.Glu386fs)	Pathogenic
2582503	NM_024077.5(SECISBP2):c.1089+2T>C	Pathogenic
2920	NM_024077.5(SECISBP2):c.1312A>T (p.Lys438Ter)	Pathogenic
2921	NM_024077.5(SECISBP2):c.1212+29G>A	Pathogenic
638567	NM_024077.5(SECISBP2):c.800dup (p.Gly268_Glu269insTer)	Pathogenic
1120062	NM_024077.5(SECISBP2):c.182+1G>A	Likely pathogenic
2631911	NM_024077.5(SECISBP2):c.2113+1G>T	Likely pathogenic
3337763	NM_024077.5(SECISBP2):c.1473_1474del (p.Gly495fs)	Likely pathogenic
3347907	NM_024077.5(SECISBP2):c.333T>G (p.Tyr111Ter)	Likely pathogenic
452802	NM_024077.5(SECISBP2):c.589C>T (p.Arg197Ter)	Likely pathogenic
452803	NM_024077.5(SECISBP2):c.283del (p.Tyr95fs)	Likely pathogenic

SpliceAI

3055 predictions. Top by Δscore:

Variant	Effect	Δscore
9:89318608:GCGAG:G	donor_gain	1.0000
9:89318610:GAG:G	donor_gain	1.0000
9:89318611:AGGT:A	donor_loss	1.0000
9:89318613:G:GA	donor_loss	1.0000
9:89318613:G:GG	donor_gain	1.0000
9:89318614:T:G	donor_loss	1.0000
9:89325895:A:AG	acceptor_gain	1.0000
9:89325896:G:GG	acceptor_gain	1.0000
9:89325896:GA:G	acceptor_gain	1.0000
9:89325896:GAA:G	acceptor_gain	1.0000
9:89325896:GAAGA:G	acceptor_gain	1.0000
9:89328649:T:TA	acceptor_gain	1.0000
9:89328652:A:AG	acceptor_gain	1.0000
9:89328653:A:G	acceptor_gain	1.0000
9:89328655:TACA:T	acceptor_loss	1.0000
9:89328656:ACAG:A	acceptor_loss	1.0000
9:89328657:CAGAT:C	acceptor_loss	1.0000
9:89328658:A:AC	acceptor_loss	1.0000
9:89328658:A:AG	acceptor_gain	1.0000
9:89328658:AGAT:A	acceptor_gain	1.0000
9:89328658:AGATG:A	acceptor_gain	1.0000
9:89328659:G:GA	acceptor_gain	1.0000
9:89328659:GA:G	acceptor_gain	1.0000
9:89328659:GAT:G	acceptor_gain	1.0000
9:89328659:GATG:G	acceptor_gain	1.0000
9:89328659:GATGG:G	acceptor_gain	1.0000
9:89328854:G:GT	donor_gain	1.0000
9:89328858:T:TA	donor_gain	1.0000
9:89328859:A:AA	donor_gain	1.0000
9:89328883:AAAG:A	donor_loss	1.0000

AlphaMissense

5593 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
9:89350682:T:C	L648P	1.000
9:89349922:T:C	F629L	0.999
9:89349923:T:C	F629S	0.999
9:89349924:C:A	F629L	0.999
9:89349924:C:G	F629L	0.999
9:89350694:T:C	L652P	0.999
9:89350712:G:C	R658P	0.999
9:89350765:G:A	G676R	0.999
9:89350765:G:C	G676R	0.999
9:89350766:G:A	G676E	0.999
9:89350790:T:C	L684P	0.999
9:89350810:T:C	C691R	0.999
9:89357476:T:C	F727L	0.999
9:89357477:T:C	F727S	0.999
9:89357478:T:A	F727L	0.999
9:89357478:T:G	F727L	0.999
9:89357480:C:A	A728D	0.999
9:89357528:T:A	V744D	0.999
9:89357530:A:C	S745R	0.999
9:89357532:T:A	S745R	0.999
9:89357532:T:G	S745R	0.999
9:89357539:G:T	G748W	0.999
9:89357540:G:A	G748E	0.999
9:89347009:G:C	R521S	0.998
9:89347009:G:T	R521S	0.998
9:89347045:G:C	K533N	0.998
9:89347045:G:T	K533N	0.998
9:89349926:G:T	R630M	0.998
9:89350638:C:G	C633W	0.998
9:89350673:T:A	V645D	0.998

dbSNP variants (sampled 300 via entrez): RS1000015045 (9:89316645 C>T), RS1000020217 (9:89319392 A>G), RS1000040581 (9:89362646 G>C), RS1000072069 (9:89360493 C>G,T), RS1000186107 (9:89343915 A>G), RS1000295951 (9:89327556 AT>A,ATT), RS1000432209 (9:89341529 T>C,G), RS1000558654 (9:89331642 A>G), RS1000708234 (9:89338834 A>G), RS1000735613 (9:89347561 C>T), RS1000785087 (9:89342520 G>A), RS1000801624 (9:89364698 C>T), RS1000878994 (9:89336410 T>C,G), RS1000906496 (9:89337485 C>T), RS1000964421 (9:89355394 C>G)

Disease associations

OMIM: gene MIM:607693 | disease phenotypes: MIM:609698

GenCC curated gene-disease

Disease	Classification	Inheritance
thyroid hormone metabolism, abnormal 1	Strong	Autosomal recessive
short stature-delayed bone age due to thyroid hormone metabolism deficiency	Supportive	Autosomal recessive

Mondo (2): thyroid hormone metabolism, abnormal 1 (MONDO:0800046), (MONDO:0012332)

Orphanet (1): Short stature-delayed bone age due to thyroid hormone metabolism deficiency (Orphanet:171706)

HPO phenotypes

22 total (22 of 22 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000508	Ptosis
HP:0000736	Short attention span
HP:0000821	Hypothyroidism
HP:0001249	Intellectual disability
HP:0001510	Growth delay
HP:0001513	Obesity
HP:0002750	Delayed skeletal maturation
HP:0002925	Elevated circulating thyroid-stimulating hormone concentration
HP:0003162	Fasting hypoglycemia
HP:0003391	Gowers sign
HP:0003623	Neonatal onset
HP:0004322	Short stature
HP:0008994	Proximal lower limb muscle weakness
HP:0009053	Distal lower limb muscle weakness
HP:0012379	Abnormal circulating enzyme concentration or activity
HP:0012548	Fatty replacement of skeletal muscle
HP:0031506	Increased circulating T4 concentration
HP:0031903	Abnormal circulating selenium concentration
HP:0032210	Decreased circulating free T3
HP:0033077	Increased circulating free T4 concentration
HP:0040214	Abnormal circulating insulin concentration

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST008154_52	Trunk fat mass	3.000000e-06

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C566454	Thyroid Hormone Metabolism, Abnormal (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, increases abundance, increases expression	3
Arsenic	affects methylation, decreases expression, increases abundance	2
bufotalin	affects expression	1
methylmercuric chloride	increases expression	1
beta-lapachone	decreases expression	1
cobaltous chloride	decreases expression	1
butyraldehyde	decreases expression	1
beta-methylcholine	affects expression	1
pentanal	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
monomethylarsonous acid	decreases expression	1
Decitabine	affects expression	1
Sunitinib	increases expression	1
Arsenic Trioxide	decreases response to substance	1
Acetaminophen	decreases expression	1
Air Pollutants	affects expression, increases abundance	1
Atrazine	decreases expression	1
Benzo(a)pyrene	increases methylation	1
Cisplatin	affects expression	1
Diethylstilbestrol	decreases expression	1
Ethyl Methanesulfonate	decreases expression	1
Hydrogen Peroxide	increases expression, affects cotreatment	1
Ketoconazole	decreases expression	1
Lead	decreases expression	1
Ozone	affects expression, increases abundance	1
Paraquat	affects splicing, increases expression	1
Phenobarbital	affects expression	1
Ribonucleotides	affects binding	1
Smoke	decreases expression	1
Theophylline	affects cotreatment, increases expression	1

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_TK49	HAP1 SECISBP2 (-)	Cancer cell line	Male

Clinical trials (associated diseases)

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