H3-5

Summary

H3-5 (H3.5 histone, HGNC:33164) is a protein-coding gene on chromosome 12p11.21, encoding Histone H3.3C (Q6NXT2). Core component of nucleosome.

Histones are basic nuclear proteins that are responsible for the nucleosome structure of the chromosomal fiber in eukaryotes. Nucleosomes consist of approximately 146 bp of DNA wrapped around a histone octamer composed of pairs of each of the four core histones (H2A, H2B, H3, and H4). The chromatin fiber is further compacted through the interaction of a linker histone, H1, with the DNA between the nucleosomes to form higher order chromatin structures. This gene contains introns and its mRNA is polyadenylated, unlike most histone genes. The protein encoded by this gene is a replication-independent histone that is a member of the histone H3 family.

Source: NCBI Gene 440093 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 28 total
• MANE Select transcript: NM_001013699

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:33164
Approved symbol	H3-5
Name	H3.5 histone
Location	12p11.21
Locus type	gene with protein product
Status	Approved
Aliases	H3.5, H3.3C
Ensembl gene	ENSG00000188375
Ensembl biotype	protein_coding
OMIM	616134
Entrez	440093

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000340398

RefSeq mRNA: 1 — MANE Select: NM_001013699 NM_001013699

CCDS: CCDS31769

Canonical transcript exons

ENST00000340398 — 1 exons

Exon	Start	End
ENSE00001378774	31791185	31792298

Expression profiles

Bgee: expression breadth ubiquitous, 102 present calls, max score 83.85.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 2.4270 / max 33.3803, expressed in 1235 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
130392	2.3905	1231
130391	0.0234	5
130390	0.0070	3
130389	0.0061	2

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
left testis	UBERON:0004533	83.85	gold quality
testis	UBERON:0000473	83.41	gold quality
right testis	UBERON:0004534	82.50	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	79.20	gold quality
stromal cell of endometrium	CL:0002255	60.94	gold quality
vermiform appendix	UBERON:0001154	59.33	gold quality
ganglionic eminence	UBERON:0004023	59.21	gold quality
cortical plate	UBERON:0005343	58.81	gold quality
placenta	UBERON:0001987	57.60	gold quality
blood	UBERON:0000178	56.95	gold quality
bone marrow	UBERON:0002371	56.57	gold quality
duodenum	UBERON:0002114	55.59	gold quality
spleen	UBERON:0002106	55.55	gold quality
ventricular zone	UBERON:0003053	53.95	gold quality
granulocyte	CL:0000094	51.54	silver quality
lymph node	UBERON:0000029	50.66	gold quality
islet of Langerhans	UBERON:0000006	47.88	gold quality
colonic epithelium	UBERON:0000397	47.33	gold quality
mucosa of transverse colon	UBERON:0004991	47.29	gold quality
bone marrow cell	CL:0002092	46.70	gold quality
tonsil	UBERON:0002372	46.58	gold quality
muscle tissue	UBERON:0002385	46.34	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	46.26	gold quality
skeletal muscle tissue	UBERON:0001134	46.14	gold quality
right coronary artery	UBERON:0001625	45.32	gold quality
tibial artery	UBERON:0007610	45.24	gold quality
popliteal artery	UBERON:0002250	45.22	gold quality
small intestine	UBERON:0002108	45.14	gold quality
skin of abdomen	UBERON:0001416	45.01	gold quality
ovary	UBERON:0000992	44.62	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	22.58
E-MTAB-8498	no	16.65
E-MTAB-6379	no	2.71

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

45 targeting H3-5, 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-3163	100.00	77.23	8605
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-128-3P	99.95	71.17	2484
HSA-MIR-216A-3P	99.95	71.19	2505
HSA-MIR-22-3P	99.93	68.13	917
HSA-MIR-1-3P	99.93	72.35	1914
HSA-MIR-206	99.93	72.50	1893
HSA-MIR-338-5P	99.92	72.34	2951
HSA-MIR-613	99.91	71.50	1710
HSA-MIR-3681-3P	99.88	70.46	2254
HSA-MIR-4496	99.88	68.89	2236
HSA-MIR-4495	99.82	72.08	3080
HSA-MIR-448	99.79	72.37	2103
HSA-MIR-3680-3P	99.75	72.51	3095
HSA-MIR-10393-3P	99.72	66.56	961
HSA-MIR-6801-5P	99.72	66.50	981
HSA-MIR-1200	99.71	70.42	1838
HSA-MIR-105-5P	99.54	69.24	2060
HSA-MIR-7853-5P	99.54	69.30	2055
HSA-MIR-409-3P	99.50	66.33	1192
HSA-MIR-6882-5P	99.35	71.13	1206
HSA-MIR-410-3P	99.27	69.98	2457
HSA-MIR-544B	99.18	67.41	1632
HSA-MIR-499A-3P	99.18	69.20	1392
HSA-MIR-4426	99.17	66.74	1949
HSA-MIR-4324	99.04	70.14	1569
HSA-MIR-3117-5P	99.04	67.93	618
HSA-MIR-1257	98.97	68.02	1133

Literature-anchored findings (GeneRIF, showing 2)

• H3.5 preferentially colocalizes with euchromatin, and it is associated with actively transcribed genes and can replace an essential function of RNAi-depleted H3.3 in cell growth. (PMID:21274551)
• H3.5 may play roles in DNA synthesis, but not apoptosis, and its expression is regulated by gonadotropins (PMID:29179259)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
rattus_norvegicus	H3f3al3	ENSRNOG00000032108
rattus_norvegicus	H3f3c	ENSRNOG00000032401
rattus_norvegicus	H3f3bl2	ENSRNOG00000067027
caenorhabditis_elegans		WBGENE00001945

Paralogs (20): CENPA (ENSG00000115163), H3-3B (ENSG00000132475), H3-3A (ENSG00000163041), H3-4 (ENSG00000168148), H3C13 (ENSG00000183598), H3C12 (ENSG00000197153), H3C4 (ENSG00000197409), H3C14 (ENSG00000203811), H3C15 (ENSG00000203852), H3Y2 (ENSG00000268799), H3Y1 (ENSG00000269466), H3-7 (ENSG00000273213), H3C8 (ENSG00000273983), H3C6 (ENSG00000274750), H3C11 (ENSG00000275379), H3C1 (ENSG00000275714), H3C7 (ENSG00000277775), H3C10 (ENSG00000278828), H3C2 (ENSG00000286522), H3C3 (ENSG00000287080)

Protein

Protein identifiers

Histone H3.3C — Q6NXT2 (reviewed: Q6NXT2)

Alternative names: Histone H3.5

All UniProt accessions (1): Q6NXT2

UniProt curated annotations — full annotation on UniProt →

Function. Core component of nucleosome. Nucleosomes wrap and compact DNA into chromatin, limiting DNA accessibility to the cellular machineries which require DNA as a template. Histones thereby play a central role in transcription regulation, DNA repair, DNA replication and chromosomal stability. DNA accessibility is regulated via a complex set of post-translational modifications of histones, also called histone code, and nucleosome remodeling. Hominid-specific H3.5/H3F3C preferentially colocalizes with euchromatin, and it is associated with actively transcribed genes.

Subunit / interactions. The nucleosome is a histone octamer containing two molecules each of H2A, H2B, H3 and H4 assembled in one H3-H4 heterotetramer and two H2A-H2B heterodimers. The octamer wraps approximately 147 bp of DNA.

Subcellular location. Nucleus. Chromosome.

Tissue specificity. Specifically expressed in the seminiferous tubules of testis.

Post-translational modifications. Acetylation is generally linked to gene activation. Acetylation on Lys-10 (H3K9ac) impairs methylation at Arg-9 (H3R8me2s). Acetylation on Lys-19 (H3K18ac) and Lys-24 (H3K24ac) favors methylation at Arg-18 (H3R17me). Acetylation at Lys-122 (H3K122ac) by EP300/p300 plays a central role in chromatin structure: localizes at the surface of the histone octamer and stimulates transcription, possibly by promoting nucleosome instability. Citrullination at Arg-9 (H3R8ci) and/or Arg-18 (H3R17ci) by PADI4 impairs methylation and represses transcription. Asymmetric dimethylation at Arg-18 (H3R17me2a) by CARM1 is linked to gene activation. Symmetric dimethylation at Arg-9 (H3R8me2s) by PRMT5 is linked to gene repression. Asymmetric dimethylation at Arg-3 (H3R2me2a) by PRMT6 is linked to gene repression and is mutually exclusive with H3 Lys-5 methylation (H3K4me2 and H3K4me3). H3R2me2a is present at the 3’ of genes regardless of their transcription state and is enriched on inactive promoters, while it is absent on active promoters. Methylation at Lys-5 (H3K4me) is linked to gene activation. Methylation at Lys-5 (H3K4me) facilitates subsequent acetylation of H3 and H4. Methylation at Lys-10 (H3K9me) and Lys-28 (H3K27me) are linked to gene repression. Methylation at Lys-10 (H3K9me) is a specific target for HP1 proteins (CBX1, CBX3 and CBX5) and prevents subsequent phosphorylation at Ser-11 (H3S10ph) and acetylation of H3 and H4. Methylation at Lys-5 (H3K4me) requires preliminary monoubiquitination of H2B at ‘Lys-120’. Methylation at Lys-10 (H3K9me) and Lys-28 (H3K27me) are enriched in inactive X chromosome chromatin. Monomethylation at Lys-56 (H3K56me1) by EHMT2/G9A in G1 phase promotes interaction with PCNA and is required for DNA replication. Phosphorylated at Thr-4 (H3T3ph) by HASPIN during prophase and dephosphorylated during anaphase. Phosphorylation at Ser-11 (H3S10ph) by AURKB is crucial for chromosome condensation and cell-cycle progression during mitosis and meiosis. In addition phosphorylation at Ser-11 (H3S10ph) by RPS6KA4 and RPS6KA5 is important during interphase because it enables the transcription of genes following external stimulation, like mitogens, stress, growth factors or UV irradiation and result in the activation of genes, such as c-fos and c-jun. Phosphorylation at Ser-11 (H3S10ph), which is linked to gene activation, prevents methylation at Lys-10 (H3K9me) but facilitates acetylation of H3 and H4. Phosphorylation at Ser-11 (H3S10ph) by AURKB mediates the dissociation of HP1 proteins (CBX1, CBX3 and CBX5) from heterochromatin. Phosphorylation at Ser-11 (H3S10ph) is also an essential regulatory mechanism for neoplastic cell transformation. Phosphorylated at Ser-29 (H3S28ph) by MAP3K20 isoform 1, RPS6KA5 or AURKB during mitosis or upon ultraviolet B irradiation. Phosphorylation at Thr-7 (H3T6ph) by PRKCB is a specific tag for epigenetic transcriptional activation that prevents demethylation of Lys-5 (H3K4me) by LSD1/KDM1A. At centromeres, specifically phosphorylated at Thr-12 (H3T11ph) from prophase to early anaphase, by DAPK3 and PKN1. Phosphorylation at Thr-12 (H3T11ph) by PKN1 or isoform M2 of PKM (PKM2) is a specific tag for epigenetic transcriptional activation that promotes demethylation of Lys-10 (H3K9me) by KDM4C/JMJD2C. Phosphorylation at Tyr-41 (H3Y41ph) by JAK2 promotes exclusion of CBX5 (HP1 alpha) from chromatin. Lysine deamination at Lys-5 (H3K4all) to form allysine is mediated by LOXL2. Allysine formation by LOXL2 only takes place on H3K4me3 and results in gene repression. Butyrylation of histones marks active promoters and competes with histone acetylation. It is present during late spermatogenesis. Succinylated. Desuccinylation at Lys-122 (H3K122succ) by SIRT7 in response to DNA damage promotes chromatin condensation and double-strand breaks (DSBs) repair. Serine ADP-ribosylation constitutes the primary form of ADP-ribosylation of proteins in response to DNA damage. Serine ADP-ribosylation at Ser-11 (H3S10ADPr) is mutually exclusive with phosphorylation at Ser-11 (H3S10ph) and impairs acetylation at Lys-10 (H3K9ac).

Similarity. Belongs to the histone H3 family.

RefSeq proteins (1): NP_001013721* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000164	Histone_H3/CENP-A	Family
IPR007125	H2A/H2B/H3	Domain
IPR009072	Histone-fold	Homologous_superfamily

Pfam: PF00125

UniProt features (109 total): modified residue 95, helix 4, cross-link 3, strand 2, initiator methionine 1, chain 1, sequence variant 1, sequence conflict 1, region of interest 1

Structure

Experimental structures (PDB)

34 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
8T4R	X-RAY DIFFRACTION	1.2
8VLF	X-RAY DIFFRACTION	1.34
2PUY	X-RAY DIFFRACTION	1.43
9C0O	X-RAY DIFFRACTION	1.53
6OI3	X-RAY DIFFRACTION	1.66
9DZN	X-RAY DIFFRACTION	1.72
7TRL	X-RAY DIFFRACTION	1.74
5I3L	X-RAY DIFFRACTION	1.85
8VLD	X-RAY DIFFRACTION	1.92
5BWN	X-RAY DIFFRACTION	1.94
9V5M	X-RAY DIFFRACTION	2.1
3KV4	X-RAY DIFFRACTION	2.19
7W67	X-RAY DIFFRACTION	2.19
8SR6	X-RAY DIFFRACTION	2.22
7W6L	X-RAY DIFFRACTION	2.26
5BWO	X-RAY DIFFRACTION	2.38
5F6K	X-RAY DIFFRACTION	2.41
7W6I	X-RAY DIFFRACTION	2.56
8Q1G	X-RAY DIFFRACTION	2.6
7W6J	X-RAY DIFFRACTION	2.68
9IM4	X-RAY DIFFRACTION	2.79
4Z5T	X-RAY DIFFRACTION	2.8
8Q1J	X-RAY DIFFRACTION	2.87
8Q1H	X-RAY DIFFRACTION	2.9
8Z73	X-RAY DIFFRACTION	2.91
8T4F	ELECTRON MICROSCOPY	3.5
9N61	ELECTRON MICROSCOPY	3.6
8RBX	ELECTRON MICROSCOPY	4.1
21GE	SOLUTION NMR
21HJ	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6NXT2-F1	86.48	0.69

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 (98): 5, 24, 5, 5, 5, 5, 6, 6, 7, 9, 9, 10, 10, 10, 10, 10, 10, 10, 10, 10 …

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 123 (showing top): GOBP_CHROMOSOME_ORGANIZATION, TTTGTAG_MIR520D, GOBP_CHROMOSOME_LOCALIZATION, GOBP_GROWTH, ATGTTAA_MIR302C, chr12p11, GOBP_NEGATIVE_REGULATION_OF_GENE_EXPRESSION_EPIGENETIC, GOBP_ORGANELLE_FISSION, GOBP_POSITIVE_REGULATION_OF_CELL_GROWTH, GOBP_MITOTIC_NUCLEAR_DIVISION, AGGAGTG_MIR483, GOBP_ORGANELLE_ASSEMBLY, GOBP_MITOTIC_CELL_CYCLE, GOBP_POSITIVE_REGULATION_OF_GROWTH, ACEVEDO_LIVER_CANCER_UP

GO Biological Process (1): positive regulation of cell growth (GO:0030307)

GO Molecular Function (5): structural constituent of chromatin (GO:0030527), nucleosomal DNA binding (GO:0031492), protein heterodimerization activity (GO:0046982), DNA binding (GO:0003677), protein binding (GO:0005515)

GO Cellular Component (5): nucleosome (GO:0000786), euchromatin (GO:0000791), nucleus (GO:0005634), nucleoplasm (GO:0005654), chromosome (GO:0005694)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
chromatin	3
regulation of cell growth	1
cell growth	1
positive regulation of growth	1
positive regulation of cellular process	1
structural molecule activity	1
chromatin DNA binding	1
nucleosome binding	1
protein dimerization activity	1
nucleic acid binding	1
binding	1
protein-DNA complex	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
cellular anatomical structure	1
intracellular membraneless organelle	1

Protein interactions and networks

STRING

8492 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
H3-5	H2AC20	Q16777	998
H3-5	H2AC19	P20670	998
H3-5	H2BC21	Q16778	998
H3-5	H4C16	P02304	997
H3-5	WDR5	P61964	997
H3-5	H4C7	Q99525	997
H3-5	CBX5	P45973	995
H3-5	DNMT3L	Q9UJW3	994
H3-5	CBX3	Q13185	991
H3-5	BRD4	O60885	989
H3-5	DNMT3A	Q9Y6K1	988
H3-5	RAG2	P55895	978
H3-5	CBX1	P23197	973
H3-5	DNMT1	P26358	973
H3-5	HDAC1	Q13547	964

IntAct

123 interactions, top by confidence:

A	B	Type	Score
NASP	H3-5	psi-mi:“MI:0915”(physical association)	0.720
H3-5	NASP	psi-mi:“MI:0915”(physical association)	0.720
H3-5	FBLIM1	psi-mi:“MI:0915”(physical association)	0.560
H3-5	DNAJC9	psi-mi:“MI:0915”(physical association)	0.560
H3-5	DAXX	psi-mi:“MI:0915”(physical association)	0.560
H3-5	CASP6	psi-mi:“MI:0915”(physical association)	0.560
H3-5	CCK	psi-mi:“MI:0915”(physical association)	0.560
H3-5	DR1	psi-mi:“MI:0915”(physical association)	0.560
H3-5		psi-mi:“MI:0915”(physical association)	0.560
H3-5	GRN	psi-mi:“MI:0915”(physical association)	0.560
H3-5	HMOX2	psi-mi:“MI:0915”(physical association)	0.560
H3-5	LAMP2	psi-mi:“MI:0915”(physical association)	0.560
H3-5	LSAMP	psi-mi:“MI:0915”(physical association)	0.560
H3-5	RAN	psi-mi:“MI:0915”(physical association)	0.560
H3-5	ICAM5	psi-mi:“MI:0915”(physical association)	0.560
H3-5	WFS1	psi-mi:“MI:0915”(physical association)	0.560
H3-5	BAG6	psi-mi:“MI:0915”(physical association)	0.560
KLF11	H3-5	psi-mi:“MI:0915”(physical association)	0.560
H3-5	GTF3C3	psi-mi:“MI:0915”(physical association)	0.560
H3-5	DNAJB6	psi-mi:“MI:0915”(physical association)	0.560
H3-5	KIF1B	psi-mi:“MI:0915”(physical association)	0.560
H3-5	RNF11	psi-mi:“MI:0915”(physical association)	0.560
H3-5	SH3GLB1	psi-mi:“MI:0915”(physical association)	0.560
H3-5	COL26A1	psi-mi:“MI:0915”(physical association)	0.560
HTT	H3-5	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (133): H3F3C (Two-hybrid), H3F3C (Affinity Capture-MS), H3F3C (Affinity Capture-MS), H3F3C (Affinity Capture-MS), H3F3C (Affinity Capture-MS), H3F3C (Affinity Capture-MS), H3F3C (Affinity Capture-MS), H3F3C (Affinity Capture-MS), H3F3C (Affinity Capture-MS), H3F3C (Affinity Capture-MS), H3F3C (Affinity Capture-MS), H3F3C (Affinity Capture-MS), H3F3C (Affinity Capture-MS), H3F3C (Co-crystal Structure), H3F3C (Affinity Capture-MS)

ESM2 similar proteins: A2XHJ3, C6Y4D0, G2TRL2, O60076, O97484, P06353, P06902, P15512, P16890, P22843, P41353, P59169, P68431, P68432, P68433, P69071, P69074, P69076, P69078, P69149, P69150, P69244, P69245, P80553, Q0JCT1, Q16695, Q22RG7, Q27489, Q27490, Q2Z2F4, Q3C2E5, Q3E835, Q55BN9, Q55BP0, Q5MYA4, Q5TEC6, Q64400, Q6LBF0, Q6LED0, Q6NXT2

Diamond homologs: A2XHJ3, A2Y533, A3LXD5, A5DFC5, A5DWE2, A5PK61, C0HL66, C0HL67, P02299, P02301, P02302, P06352, P08437, P08898, P08903, P09988, P22843, P59169, P59226, P68427, P68428, P68429, P68430, P68431, P68432, P68433, P69071, P69072, P69073, P69074, P69075, P69076, P69077, P69078, P69079, P69244, P69245, P69246, P69248, P80553

SIGNOR signaling

13 interactions.

A	Effect	B	Mechanism
SLBP	“up-regulates quantity by expression”	H3-5	“translation regulation”
BAZ2B	“down-regulates activity”	H3-5	binding
Sin3B_complex	“down-regulates activity”	H3-5	binding
KAT2A	“down-regulates activity”	H3-5	acetylation
KAT2B	“down-regulates activity”	H3-5	acetylation
“SAGA complex”	“down-regulates activity”	H3-5	acetylation
KDM3A	“up-regulates activity”	H3-5	demethylation
SIRT7	“up-regulates activity”	H3-5	deacetylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 56 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
Chromatin organization	8	15.5×	1e-05
Chromatin modifying enzymes	8	13.8×	1e-05

GO biological processes:

GO term	Partners	Fold	FDR
methylation	6	20.0×	2e-04
chromatin remodeling	7	10.0×	1e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	28
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

211 predictions. Top by Δscore:

Variant	Effect	Δscore
12:31791761:AAG:A	donor_gain	0.6800
12:31791751:G:GA	donor_gain	0.6500
12:31792001:T:TA	donor_gain	0.6400
12:31791761:AAGCT:A	donor_gain	0.6200
12:31791762:A:C	donor_gain	0.6000
12:31791755:TC:T	donor_gain	0.5800
12:31791761:A:AC	donor_gain	0.5800
12:31792172:TTC:T	donor_gain	0.5800
12:31792085:T:A	donor_gain	0.5600
12:31791755:T:TA	donor_gain	0.5400
12:31792123:TTCCC:T	donor_gain	0.5300
12:31791653:T:C	acceptor_gain	0.5200
12:31792137:T:C	donor_gain	0.5200
12:31791771:T:A	donor_gain	0.5000
12:31791950:C:CA	donor_gain	0.5000
12:31791953:TCAC:T	donor_loss	0.4900
12:31791954:CACC:C	donor_loss	0.4900
12:31791955:ACCA:A	donor_loss	0.4900
12:31791957:CAAC:C	donor_loss	0.4900
12:31791958:AAC:A	donor_loss	0.4900
12:31791959:A:T	donor_loss	0.4900
12:31791960:C:A	donor_loss	0.4900
12:31791629:ATC:A	acceptor_loss	0.4800
12:31791633:T:A	acceptor_loss	0.4800
12:31791961:C:G	donor_loss	0.4800
12:31791977:T:TA	donor_gain	0.4800
12:31791952:CTCA:C	donor_loss	0.4600
12:31791962:T:A	donor_loss	0.4400
12:31791730:C:CT	donor_gain	0.4300
12:31791731:T:TT	donor_gain	0.4300

AlphaMissense

858 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:31791799:T:G	D123A	0.985
12:31791800:C:G	D123H	0.983
12:31791799:T:A	D123V	0.979
12:31791798:G:C	D123E	0.978
12:31791798:G:T	D123E	0.978
12:31791835:G:T	A111D	0.975
12:31791819:T:A	R116S	0.970
12:31791819:T:G	R116S	0.970
12:31791966:G:C	F67L	0.970
12:31791966:G:T	F67L	0.970
12:31791968:A:G	F67L	0.970
12:31791787:G:T	A127D	0.969
12:31791915:A:C	F84L	0.968
12:31791915:A:T	F84L	0.968
12:31791917:A:G	F84L	0.968
12:31792002:C:A	Q55H	0.968
12:31792002:C:G	Q55H	0.968
12:31791781:C:G	R129P	0.967
12:31791836:C:G	A111P	0.966
12:31791879:G:C	S96R	0.964
12:31791879:G:T	S96R	0.964
12:31791881:T:G	S96R	0.964
12:31791820:C:A	R116I	0.963
12:31791784:C:G	R128P	0.961
12:31791799:T:C	D123G	0.961
12:31791837:A:C	C110W	0.959
12:31792012:C:G	R52P	0.958
12:31792036:C:T	G44E	0.957
12:31791820:C:G	R116T	0.956
12:31791875:C:G	A98P	0.955

dbSNP variants (sampled 300 via entrez): RS1000549714 (12:31793464 G>A), RS1001172982 (12:31793754 C>T), RS1001648883 (12:31791538 T>C), RS1003067887 (12:31792420 C>A,T), RS1004397396 (12:31793249 A>T), RS1004449824 (12:31792861 A>G), RS1005245309 (12:31792791 G>A), RS1005451814 (12:31794158 T>C), RS1005840436 (12:31794108 G>A), RS1009193995 (12:31794062 T>C), RS1010958503 (12:31793587 C>A,T), RS1011010680 (12:31793328 C>A,T), RS1011252948 (12:31792344 C>A,T), RS1013659322 (12:31792414 C>T), RS1014033937 (12:31794145 C>G,T)

Disease associations

OMIM: gene MIM:616134 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

10 total (human), top 10 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	affects cotreatment, increases abundance, increases expression	1
manganese chloride	affects cotreatment, increases abundance, increases expression	1
perfluorooctane sulfonic acid	decreases expression	1
Arsenic	affects cotreatment, increases abundance, increases expression	1
Benzo(a)pyrene	decreases expression	1
Doxorubicin	affects expression	1
Manganese	affects cotreatment, increases abundance, increases expression	1
Rotenone	increases expression	1
Aflatoxin B1	decreases methylation	1
Lactic Acid	affects expression	1

Clinical trials (associated diseases)

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