SELENOH

Summary

SELENOH (selenoprotein H, HGNC:18251) is a protein-coding gene on chromosome 11q12.1, encoding Selenoprotein H (Q8IZQ5). May be involved in a redox-related process.

This gene encodes a nucleolar protein, which belongs to the SelWTH family. It functions as an oxidoreductase, and has been shown to protect neurons against UVB-induced damage by inhibiting apoptotic cell death pathways, promote mitochondrial biogenesis and mitochondrial function, and suppress cellular senescence through genome maintenance and redox regulation. This protein is a selenoprotein, containing the rare amino acid selenocysteine (Sec) at its active site. Sec is encoded by the UGA codon, which normally signals translation termination. The 3’ UTRs of selenoprotein mRNAs contain a conserved stem-loop structure, designated the Sec insertion sequence (SECIS) element, that is necessary for the recognition of UGA as a Sec codon, rather than as a stop signal. Alternatively spliced transcript variants have been found for this gene.

Source: NCBI Gene 280636 — RefSeq curated summary.

At a glance

• GWAS associations: 5
• Clinical variants (ClinVar): 3 total
• MANE Select transcript: NM_170746

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:18251
Approved symbol	SELENOH
Name	selenoprotein H
Location	11q12.1
Locus type	gene with protein product
Status	Approved
Aliases	SELH
Ensembl gene	ENSG00000211450
Ensembl biotype	protein_coding
OMIM	607914
Entrez	280636

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 3 protein_coding, 2 retained_intron, 1 TEC

ENST00000388857, ENST00000528798, ENST00000533321, ENST00000534355, ENST00000534386, ENST00000623303

RefSeq mRNA: 2 — MANE Select: NM_170746 NM_001321335, NM_170746

CCDS: CCDS44602

Canonical transcript exons

ENST00000534355 — 4 exons

Exon	Start	End
ENSE00001504178	57741809	57741954
ENSE00002162408	57741491	57741717
ENSE00003605266	57742117	57742247
ENSE00003843202	57742863	57743550

Expression profiles

Bgee: expression breadth ubiquitous, 230 present calls, max score 97.97.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 164.7508 / max 856.0765, expressed in 1827 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
114323	82.7443	1822
114321	45.9114	1823
114322	36.0951	1809

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right adrenal gland cortex	UBERON:0035827	97.97	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	97.94	gold quality
right adrenal gland	UBERON:0001233	97.87	gold quality
left adrenal gland cortex	UBERON:0035825	97.87	gold quality
left adrenal gland	UBERON:0001234	97.75	gold quality
adenohypophysis	UBERON:0002196	97.38	gold quality
right uterine tube	UBERON:0001302	97.14	gold quality
lower esophagus mucosa	UBERON:0035834	97.10	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	97.06	gold quality
right lobe of liver	UBERON:0001114	97.03	gold quality
ganglionic eminence	UBERON:0004023	97.01	gold quality
right frontal lobe	UBERON:0002810	96.80	gold quality
mucosa of transverse colon	UBERON:0004991	96.79	gold quality
left lobe of thyroid gland	UBERON:0001120	96.74	gold quality
anterior cingulate cortex	UBERON:0009835	96.74	gold quality
right lobe of thyroid gland	UBERON:0001119	96.58	gold quality
metanephros cortex	UBERON:0010533	96.55	gold quality
ventricular zone	UBERON:0003053	96.54	gold quality
Brodmann (1909) area 9	UBERON:0013540	96.42	gold quality
leukocyte	CL:0000738	96.38	gold quality
monocyte	CL:0000576	96.37	gold quality
body of pancreas	UBERON:0001150	96.36	gold quality
minor salivary gland	UBERON:0001830	96.15	gold quality
endocervix	UBERON:0000458	96.14	gold quality
right atrium auricular region	UBERON:0006631	96.13	gold quality
left ovary	UBERON:0002119	96.11	gold quality
granulocyte	CL:0000094	96.10	gold quality
cortical plate	UBERON:0005343	96.09	gold quality
body of stomach	UBERON:0001161	96.05	gold quality
prefrontal cortex	UBERON:0000451	96.01	gold quality

Single-cell (SCXA)

Detected in 5 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-MTAB-9221	yes	423.04
E-ANND-3	yes	16.39
E-MTAB-10042	yes	13.34
E-MTAB-8205	no	717.63
E-HCAD-8	no	41.86

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): NKX3-1

miRNA regulators (miRDB)

38 targeting SELENOH, 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-29A-3P	100.00	73.11	1835
HSA-MIR-29B-3P	100.00	73.18	1833
HSA-MIR-29C-3P	100.00	73.15	1833
HSA-MIR-6780A-5P	99.88	66.69	2776
HSA-MIR-3140-3P	99.88	68.47	2069
HSA-MIR-1273H-5P	99.77	66.32	2471
HSA-MIR-2116-3P	99.74	64.32	889
HSA-MIR-4699-3P	99.71	70.15	3142
HSA-MIR-30B-3P	99.70	65.76	2325
HSA-MIR-3689A-3P	99.70	65.73	2306
HSA-MIR-3689B-3P	99.70	65.71	2311
HSA-MIR-3689C	99.70	65.71	2311
HSA-MIR-6779-5P	99.70	65.76	2363
HSA-MIR-1207-5P	99.49	69.11	2983
HSA-MIR-508-5P	99.41	64.25	1248
HSA-MIR-888-5P	99.30	70.15	1855
HSA-MIR-4721	99.26	66.05	818
HSA-MIR-149-5P	99.25	67.16	1315
HSA-MIR-6799-5P	99.14	65.72	2093
HSA-MIR-6815-3P	99.13	68.98	1530
HSA-MIR-4763-3P	99.10	67.83	2649
HSA-MIR-6868-5P	99.06	65.69	1284
HSA-MIR-548S	98.50	67.17	1213
HSA-MIR-532-5P	98.43	67.53	760
HSA-MIR-1262	98.17	66.52	757
HSA-MIR-4701-3P	98.17	66.25	788
HSA-MIR-6736-5P	98.17	66.43	760
HSA-MIR-7113-5P	97.88	67.33	1735
HSA-MIR-4433A-3P	97.75	62.82	1435
HSA-MIR-510-5P	97.66	65.82	916

Literature-anchored findings (GeneRIF, showing 11)

• SelH is a novel nucleolar oxidoreductase that may have functions which are regulated by redox and dependent on the trace element selenium (PMID:17337453)
• hSelH overexpression protects cells from UVB irradiation-induced murine hippocampal neuronal cell death by reducing the superoxide formation. (PMID:17389926)
• selenoprotein H is a redox-responsive DNA-binding protein of the AT-hook family and functions in regulating expression levels of genes involved in de novo glutathione synthesis and phase II detoxification in response to redox status. (PMID:17526492)
• t SelH protects neurons against UVB-induced damage by inhibiting apoptotic cell death pathways (PMID:19766117)
• Overexpression of SelH promotes mitochondrial biogenesis and improves mitochondrial functional performance. (PMID:20656065)
• We conclude that the effects of selenoprotein H on mitochondrial biogenesis and mitochondrial function are probably mediated through protein kinase A-CREB-PGC-1alpha and Akt/protein kinase B-CREB-PGC-1alpha pathways. (PMID:23220172)
• Selenoprotein H suppresses cellular senescence through genome maintenance and redox regulation. (PMID:25336634)
• Transcriptome analysis revealed that SepH deficiency induces an inflammatory response and activates the p53 pathway. Consequently, loss of seph renders larvae susceptible to oxidative stress and DNA damage. Finally, we demonstrate that seph interacts with p53 deficiency in adulthood to accelerate gastrointestinal tumor development (PMID:27588899)
• The high levels of SELENOH in tumors as well as in undifferentiated, proliferative cells together with its inhibitory effects on proliferation and G1/S phase transition suggest SELENOH as a key regulator for cell cycle progression and for prevention of uncontrolled proliferation (PMID:29330096)
• the obtained results clearly illustrate Sec residue plays an important role to restore functionally active conformation of SELENOH. The present study broadened our current understanding regarding the role of selenocysteine in protein structure and function. (PMID:29480333)
• Identification of Selenoprotein H Isoforms and Impact of Selenoprotein H Overexpression on Protein But Not mRNA Levels of 2 Other Selenoproteins in 293T Cells. (PMID:34510207)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
drosophila_melanogaster	CG15147	FBGN0032654
drosophila_melanogaster	CG13186	FBGN0033680

Protein

Protein identifiers

Selenoprotein H — Q8IZQ5 (reviewed: Q8IZQ5)

All UniProt accessions (2): Q8IZQ5, H0YE28

UniProt curated annotations — full annotation on UniProt →

Function. May be involved in a redox-related process.

Similarity. Belongs to the SelWTH family.

RefSeq proteins (2): NP_001308264, NP_734467* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR011893	Selenoprotein_Rdx-typ	Family
IPR036249	Thioredoxin-like_sf	Homologous_superfamily
IPR052674	SelWTH-like	Family

Pfam: PF10262

UniProt features (4 total): chain 1, non-standard amino acid 1, modified residue 1, cross-link 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

No AlphaFold model available for Q8IZQ5 — AlphaFold DB does not currently provide models for proteins above ~3000 aa.

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 (2): 20, 41–44

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 159 (showing top): STARK_PREFRONTAL_CORTEX_22Q11_DELETION_DN, AAGCCAT_MIR135A_MIR135B, RACCACAR_AML_Q6, AML1_01, CUI_TCF21_TARGETS_2_UP, GOBERT_OLIGODENDROCYTE_DIFFERENTIATION_UP, KRIEG_HYPOXIA_VIA_KDM3A, KRIEG_HYPOXIA_NOT_VIA_KDM3A, RAO_BOUND_BY_SALL4_ISOFORM_B, RB_P130_DN.V1_UP, ALKBH3_TARGET_GENES, CBX5_TARGET_GENES, DIDO1_TARGET_GENES, DLX4_TARGET_GENES, GLI4_TARGET_GENES

GO Biological Process (0):

GO Molecular Function (1): RNA binding (GO:0003723)

GO Cellular Component (1): Golgi apparatus (GO:0005794)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
nucleic acid binding	1
cytoplasm	1
endomembrane system	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

422 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SELENOH	SELENOT	P62341	886
SELENOH	SELENOK	Q9Y6D0	878
SELENOH	SELENOV	P59797	852
SELENOH	SELENOF	O60613	841
SELENOH	SELENOO	Q9BVL4	831
SELENOH	SELENOW	P63302	824
SELENOH	SELENOS	Q9BQE4	822
SELENOH	SEPHS2	Q99611	821
SELENOH	SELENOI	Q9C0D9	807
SELENOH	SELENOM	Q8WWX9	801
SELENOH	SELENON	Q9NZV5	796
SELENOH	MSRB1	Q9NZV6	787
SELENOH	TXNRD3	Q86VQ6	779
SELENOH	TXNRD2	Q9NNW7	745
SELENOH	TXNRD1	Q16881	721

IntAct

36 interactions, top by confidence:

A	B	Type	Score
CPSF6	NUDT21	psi-mi:“MI:0914”(association)	0.890
ACBD6	NMT2	psi-mi:“MI:0914”(association)	0.870
PIP4K2A	AP3B1	psi-mi:“MI:0914”(association)	0.530
ARIH1	SPOP	psi-mi:“MI:0914”(association)	0.530
GHITM	CCNB2	psi-mi:“MI:0914”(association)	0.530
Arhgef3	SELENOH	psi-mi:“MI:0915”(physical association)	0.400
PPP1R14C	SELENOH	psi-mi:“MI:0915”(physical association)	0.400
FYB1	CKAP5	psi-mi:“MI:0914”(association)	0.350
HTRA4	PSMD12	psi-mi:“MI:0914”(association)	0.350
BMI1	HMGB1P1	psi-mi:“MI:0914”(association)	0.350
MAPT	SHTN1	psi-mi:“MI:0914”(association)	0.350
KPNA4	POM121C	psi-mi:“MI:0914”(association)	0.350
PPM1G	SRP14	psi-mi:“MI:0914”(association)	0.350
MYH4	PALM3	psi-mi:“MI:0914”(association)	0.350
MKRN1	GAPDHS	psi-mi:“MI:0914”(association)	0.350
H2AC11	U2SURP	psi-mi:“MI:0914”(association)	0.350
ARIH1	PHGDH	psi-mi:“MI:0914”(association)	0.350
SALL1	MTA2	psi-mi:“MI:0914”(association)	0.350
SHISA6	KLHL18	psi-mi:“MI:0914”(association)	0.350
ARID4A	FRYL	psi-mi:“MI:0914”(association)	0.350
PIGO	HRAS	psi-mi:“MI:0914”(association)	0.350
DEFB116	SRC	psi-mi:“MI:0914”(association)	0.350
PTPRZ1	ACTA2	psi-mi:“MI:0914”(association)	0.350
GSX2	RNF4	psi-mi:“MI:0914”(association)	0.350
CNGA1	WWC1	psi-mi:“MI:0914”(association)	0.350
CEBPA	HAX1	psi-mi:“MI:0914”(association)	0.350

BioGRID (43): C11orf31 (Proximity Label-MS), C11orf31 (Affinity Capture-MS), C11orf31 (Affinity Capture-MS), C11orf31 (Affinity Capture-MS), C11orf31 (Affinity Capture-MS), C11orf31 (Affinity Capture-MS), C11orf31 (Affinity Capture-MS), C11orf31 (Proximity Label-MS), C11orf31 (Affinity Capture-RNA), C11orf31 (Affinity Capture-MS), C11orf31 (Affinity Capture-MS), C11orf31 (Affinity Capture-MS), C11orf31 (Affinity Capture-MS), C11orf31 (Affinity Capture-MS), C11orf31 (Affinity Capture-MS)

ESM2 similar proteins: A8WH18, B0VXH3, B1MT69, B4FHF0, B5X5B4, B8BAI9, B9SEZ6, O19097, O43678, P0CB79, P0CB80, P13621, P52827, P63300, P63301, P63302, P63303, P99029, Q02370, Q02784, Q06647, Q07842, Q0JQ97, Q0MQ92, Q1JQD4, Q3UQA7, Q4R5E2, Q4R5Y4, Q5NVB2, Q5ZJN8, Q6GP98, Q6PBD1, Q6PBM1, Q6X4M2, Q6ZJS7, Q7S300, Q7SGH0, Q7YR75, Q80Y14, Q8IZQ5

Diamond homologs: Q3UQA7, Q4R5Y4, Q8IZQ5, Q9VYB0

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	2
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

840 predictions. Top by Δscore:

Variant	Effect	Δscore
11:57741692:G:GT	donor_gain	1.0000
11:57741731:A:T	donor_gain	1.0000
11:57741807:A:AG	acceptor_gain	1.0000
11:57741808:G:GT	acceptor_gain	1.0000
11:57741808:GC:G	acceptor_gain	1.0000
11:57741808:GCA:G	acceptor_gain	1.0000
11:57741808:GCACT:G	acceptor_gain	1.0000
11:57741951:AGCA:A	donor_gain	1.0000
11:57741952:GCA:G	donor_gain	1.0000
11:57741952:GCAG:G	donor_gain	1.0000
11:57741953:CA:C	donor_gain	1.0000
11:57741954:AG:A	donor_loss	1.0000
11:57741955:G:GG	donor_gain	1.0000
11:57741956:T:A	donor_loss	1.0000
11:57742202:G:GT	donor_gain	1.0000
11:57742205:G:GG	donor_gain	1.0000
11:57742218:G:GT	donor_gain	1.0000
11:57742862:GCTTT:G	acceptor_gain	1.0000
11:57742967:T:G	donor_gain	1.0000
11:57742985:G:GG	donor_gain	1.0000
11:57741715:TTG:T	donor_gain	0.9900
11:57741718:G:GA	donor_loss	0.9900
11:57741718:G:GG	donor_gain	0.9900
11:57741719:T:G	donor_loss	0.9900
11:57741807:A:AT	acceptor_loss	0.9900
11:57741808:GCAC:G	acceptor_gain	0.9900
11:57741810:A:AG	acceptor_gain	0.9900
11:57741950:CAGCA:C	donor_gain	0.9900
11:57741957:AA:A	donor_loss	0.9900
11:57741958:A:AG	donor_gain	0.9900

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1001146171 (11:57740619 A>G,T), RS1001289016 (11:57741831 C>T), RS1001410718 (11:57740822 G>A), RS1002258764 (11:57741022 G>A,T), RS1002933554 (11:57742619 AAC>A), RS1003144091 (11:57742623 C>T), RS1003375404 (11:57743059 T>A), RS1004961345 (11:57743422 G>A), RS1005289624 (11:57743644 T>G), RS1005395513 (11:57743710 A>C), RS1006314838 (11:57742439 A>C,G), RS1006800301 (11:57742614 G>A), RS1007093643 (11:57740838 G>A,C), RS1007145136 (11:57740535 A>C,G), RS1007501025 (11:57741938 G>A,T)

Disease associations

OMIM: gene MIM:607914 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

5 associations (top):

Study	Trait	p-value
GCST002539_6	Schizophrenia	2.000000e-09
GCST004521_290	Autism spectrum disorder or schizophrenia	5.000000e-08
GCST004946_35	Schizophrenia	9.000000e-09
GCST005232_71	Neuroticism	7.000000e-11
GCST006803_71	Schizophrenia	1.000000e-09

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0007660	neuroticism measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

23 total (human), top 23 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
dicrotophos	decreases expression	1
methylmercuric chloride	decreases expression	1
beta-lapachone	decreases expression	1
sulforaphane	decreases expression	1
sodium arsenite	decreases expression	1
cobaltous chloride	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
selenium tetrachloride	increases expression	1
monomethylarsonous acid	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
LDN 193189	affects cotreatment, increases expression	1
3-(2-hydroxy-4-(2-methylnonan-2-yl)phenyl)cyclohexan-1-ol	decreases expression	1
Benzo(a)pyrene	affects methylation	1
Doxorubicin	increases expression	1
Estradiol	decreases expression	1
Hydrogen Peroxide	decreases response to substance, increases expression, increases reaction, increases phosphorylation	1
Ivermectin	decreases expression	1
Paraquat	decreases response to substance	1
Smoke	decreases expression	1
Superoxides	decreases abundance	1
Urethane	decreases expression	1
Valproic Acid	affects expression	1
Vincristine	decreases expression	1

Cellosaurus cell lines

1 cell lines: 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B3GR	Abcam HEK293T SELENOH KO	Transformed cell line	Female

Clinical trials (associated diseases)

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