NCAPH2

Summary

NCAPH2 (non-SMC condensin II complex subunit H2, HGNC:25071) is a protein-coding gene on chromosome 22q13.33, encoding Condensin-2 complex subunit H2 (Q6IBW4). Regulatory subunit of the condensin-2 complex, a complex that seems to provide chromosomes with an additional level of organization and rigidity and in establishing mitotic chromosome architecture. It is a selective cancer dependency (DepMap: 80.8% of cell lines).

This gene encodes one of the non-SMC subunits of the condensin II complex. This complex plays an essential role in mitotic chromosome assembly. Alternate splicing of this gene results in multiple transcript variants.

Source: NCBI Gene 29781 — RefSeq curated summary.

At a glance

• GWAS associations: 10
• Clinical variants (ClinVar): 497 total — 21 pathogenic, 10 likely-pathogenic
• Cancer dependency (DepMap): dependent in 80.8% of screened cell lines
• MANE Select transcript: NM_152299

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:25071
Approved symbol	NCAPH2
Name	non-SMC condensin II complex subunit H2
Location	22q13.33
Locus type	gene with protein product
Status	Approved
Aliases	384D8-2, hCAP-H2, CAP-H2
Ensembl gene	ENSG00000025770
Ensembl biotype	protein_coding
OMIM	611230
Entrez	29781

Gene structure

Transcript identifiers

Ensembl transcripts: 44 — 40 protein_coding, 2 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined, 1 retained_intron

ENST00000299821, ENST00000395698, ENST00000395701, ENST00000418794, ENST00000420993, ENST00000518394, ENST00000520297, ENST00000522048, ENST00000522304, ENST00000523045, ENST00000910456, ENST00000910457, ENST00000910458, ENST00000910459, ENST00000910460, ENST00000910461, ENST00000910462, ENST00000910463, ENST00000910464, ENST00000910465, ENST00000910466, ENST00000910467, ENST00000910468, ENST00000910469, ENST00000910470, ENST00000910471, ENST00000924783, ENST00000924784, ENST00000924785, ENST00000924786, ENST00000954521, ENST00000954522, ENST00000954523, ENST00000954524, ENST00000954525, ENST00000954526, ENST00000954527, ENST00000954528, ENST00000954529, ENST00000954530, ENST00000954531, ENST00000954532, ENST00000954533, ENST00000954534

RefSeq mRNA: 3 — MANE Select: NM_152299 NM_001185011, NM_014551, NM_152299

CCDS: CCDS14094, CCDS43038, CCDS54546

Canonical transcript exons

ENST00000420993 — 20 exons

Exon	Start	End
ENSE00001681925	50508224	50508445
ENSE00003248700	50522821	50522922
ENSE00003251329	50518133	50518278
ENSE00003252877	50522671	50522720
ENSE00003284394	50518649	50518732
ENSE00003298230	50519190	50519320
ENSE00003374474	50523017	50523166
ENSE00003479623	50517741	50517809
ENSE00003519945	50516447	50516548
ENSE00003557802	50521741	50521848
ENSE00003562448	50522501	50522569
ENSE00003563851	50517577	50517661
ENSE00003574733	50522181	50522251
ENSE00003586268	50522343	50522415
ENSE00003587020	50521986	50522039
ENSE00003600900	50517427	50517482
ENSE00003644256	50520965	50521036
ENSE00003674580	50517973	50518052
ENSE00003690410	50521543	50521609
ENSE00003847714	50523235	50524780

Expression profiles

Bgee: expression breadth ubiquitous, 260 present calls, max score 94.57.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 19.1050 / max 141.9341, expressed in 1804 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
193005	18.0382	1803
193006	1.0668	565

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
cerebellar hemisphere	UBERON:0002245	94.57	gold quality
right hemisphere of cerebellum	UBERON:0014890	94.54	gold quality
cerebellar cortex	UBERON:0002129	94.49	gold quality
right testis	UBERON:0004534	94.33	gold quality
left testis	UBERON:0004533	94.01	gold quality
ventricular zone	UBERON:0003053	93.76	gold quality
vena cava	UBERON:0004087	93.45	silver quality
cerebellum	UBERON:0002037	93.15	gold quality
ganglionic eminence	UBERON:0004023	93.15	gold quality
adenohypophysis	UBERON:0002196	92.91	gold quality
type B pancreatic cell	CL:0000169	92.89	gold quality
apex of heart	UBERON:0002098	92.69	gold quality
right frontal lobe	UBERON:0002810	92.53	gold quality
pituitary gland	UBERON:0000007	92.14	gold quality
granulocyte	CL:0000094	92.09	gold quality
left ovary	UBERON:0002119	92.08	gold quality
lower esophagus mucosa	UBERON:0035834	91.84	gold quality
left uterine tube	UBERON:0001303	91.73	gold quality
right ovary	UBERON:0002118	91.69	gold quality
anterior cingulate cortex	UBERON:0009835	91.50	gold quality
cingulate cortex	UBERON:0003027	91.49	gold quality
prefrontal cortex	UBERON:0000451	91.33	gold quality
ectocervix	UBERON:0012249	91.31	gold quality
body of uterus	UBERON:0009853	91.29	gold quality
testis	UBERON:0000473	91.07	gold quality
body of pancreas	UBERON:0001150	90.97	gold quality
hindlimb stylopod muscle	UBERON:0004252	90.97	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	90.96	gold quality
upper lobe of left lung	UBERON:0008952	90.95	gold quality
endocervix	UBERON:0000458	90.92	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-MTAB-9543	yes	42.96
E-CURD-112	yes	8.91
E-ANND-3	yes	6.09

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

41 targeting NCAPH2, 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-6867-5P	100.00	82.21	3464
HSA-MIR-4692	100.00	67.32	2066
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-32-5P	99.98	75.21	1964
HSA-MIR-92A-3P	99.98	75.21	1960
HSA-MIR-92B-3P	99.98	75.25	1955
HSA-MIR-25-3P	99.98	74.60	1817
HSA-MIR-363-3P	99.98	74.72	1821
HSA-MIR-367-3P	99.98	74.83	1819
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-6794-5P	99.76	66.38	1048
HSA-MIR-6764-5P	99.75	67.89	2304
HSA-MIR-518A-5P	99.70	69.01	2209
HSA-MIR-527	99.70	69.01	2209
HSA-MIR-4716-3P	99.69	66.73	1022
HSA-MIR-3934-5P	99.67	64.04	846
HSA-MIR-4516	99.61	67.78	3390
HSA-MIR-6132	99.60	65.83	1554
HSA-MIR-6836-5P	99.60	65.62	1538
HSA-MIR-1915-3P	99.58	66.79	1988
HSA-MIR-6839-3P	99.39	68.86	1301
HSA-MIR-6791-5P	99.16	65.92	1844
HSA-MIR-6770-5P	98.97	66.76	1853
HSA-MIR-629-5P	98.78	68.72	1032
HSA-MIR-3691-5P	98.62	65.88	552
HSA-MIR-4726-3P	98.49	63.89	1385
HSA-MIR-6880-5P	98.08	65.59	1282
HSA-MIR-4303	98.01	68.13	2304
HSA-MIR-3665	97.73	65.08	975

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 80.8% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 10)

• The CAP-H2 subunit of the condensin II complex implicated in chromosome assembly and segregation (PMID:14532007)
• CAPH2 protein accumulates as cells approach senescence, and knockdown of CAPH2 inhibits senescence. (PMID:26017022)
• DNA methylation in the NCAPH2/LMF2 promoter region is significantly decreased in Alzheimer disease. (PMID:26742120)
• Results suggest that DNA methylation in the NCAPH2/LMF2 promoter region is associated with hippocampal atrophy through apoptosis (PMID:27356276)
• Data found that the abundance of CAP-H2 is increased in mitosis by a Plk1 kinase activity-dependent manner and that inhibition of Plk1 induces a degradation of CAP-H2 through Cdc20-mediated ubiquitin-proteasome machinery. These results suggest that the expression levels of CAP-H2 are regulated by Plk1 and Cdc20 for proper chromosomal organization during mitosis. (PMID:28717250)
• Condensin II(CAP-D3 and CAP-H2) and GAIT subunits associate with L1 RNA in a co-dependent manner, independent of IFN-gamma. These findings suggest that cooperation between the Condensin II and GAIT complexes may facilitate a novel mechanism of L1 repression, thus contributing to the maintenance of genome stability in somatic cells (PMID:29028794)
• NCAPH2 promotes telomere stability, possibly through a direct interaction with the TRF1 shelterin component (PMID:31026066)
• Cancer-associated mutations in the condensin II subunit CAPH2 cause genomic instability through telomere dysfunction and anaphase chromosome bridges. (PMID:33078399)
• OCT1 Is a Poor Prognostic Factor for Breast Cancer Patients and Promotes Cell Proliferation via Inducing NCAPH. (PMID:34768935)
• Associations Between Levels of Peripheral NCAPH2 Promoter Methylation and Different Stages of Alzheimer’s Disease: A Cross-Sectional Study. (PMID:36806511)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	ncaph2	ENSDARG00000033757
mus_musculus	Ncaph2	ENSMUSG00000008690
rattus_norvegicus	Ncaph2	ENSRNOG00000009598
caenorhabditis_elegans		WBGENE00016202

Protein

Protein identifiers

Condensin-2 complex subunit H2 — Q6IBW4 (reviewed: Q6IBW4)

Alternative names: Chromosome-associated protein H2, Kleisin-beta, Non-SMC condensin II complex subunit H2

All UniProt accessions (6): A0A0A6YYG7, E5RJL4, E5RJN3, Q6IBW4, F8WAR3, H0YC55

UniProt curated annotations — full annotation on UniProt →

Function. Regulatory subunit of the condensin-2 complex, a complex that seems to provide chromosomes with an additional level of organization and rigidity and in establishing mitotic chromosome architecture. May promote the resolution of double-strand DNA catenanes (intertwines) between sister chromatids. Condensin-mediated compaction likely increases tension in catenated sister chromatids, providing directionality for type II topoisomerase-mediated strand exchanges toward chromatid decatenation. Required for decatenation of chromatin bridges at anaphase. Early in neurogenesis, may play an essential role to ensure accurate mitotic chromosome condensation in neuron stem cells, ultimately affecting neuron pool and cortex size. Seems to have lineage-specific role in T-cell development.

Subunit / interactions. Component of the condensin-2 complex, which contains the SMC2 and SMC4 heterodimer, and three non SMC subunits, NCAPG2, NCAPH2 and NCAPD3 that probably regulate the complex.

Subcellular location. Nucleus. Chromosome.

Similarity. Belongs to the CND2 H2 (condensin-2 subunit 2) family.

Isoforms (4)

UniProt ID	Names	Canonical?
Q6IBW4-1	1	yes
Q6IBW4-2	2
Q6IBW4-5	3
Q6IBW4-4	4

RefSeq proteins (3): NP_001171940, NP_055366, NP_689512* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR009378	H2_N	Domain
IPR031719	H2_M	Domain
IPR031737	CNDH2_C	Domain
IPR031739	Ncaph2	Family

Pfam: PF06278, PF16858, PF16869

UniProt features (30 total): sequence conflict 13, modified residue 10, splice variant 4, chain 1, region of interest 1, compositionally biased region 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
9F5W	ELECTRON MICROSCOPY	7.5

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6IBW4-F1	63.22	0.14

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 (10): 284, 466, 492, 19, 95, 200, 208, 228, 232, 282

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-2299718	Condensation of Prophase Chromosomes

MSigDB gene sets: 0 (showing top):

GO Biological Process (10): mitotic chromosome condensation (GO:0007076), meiotic chromosome condensation (GO:0010032), T cell differentiation in thymus (GO:0033077), mitotic sister chromatid separation (GO:0051306), female meiosis chromosome separation (GO:0051309), positive regulation of chromosome segregation (GO:0051984), positive regulation of chromosome separation (GO:1905820), positive regulation of chromosome condensation (GO:1905821), female meiotic nuclear division (GO:0007143), chromosome condensation (GO:0030261)

GO Molecular Function (2): chromatin binding (GO:0003682), protein binding (GO:0005515)

GO Cellular Component (9): condensed nuclear chromosome (GO:0000794), condensin complex (GO:0000796), nucleus (GO:0005634), nucleoplasm (GO:0005654), membrane (GO:0016020), cell junction (GO:0030054), intercellular bridge (GO:0045171), condensed chromosome (GO:0000793), chromosome (GO:0005694)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Mitotic Prophase	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
chromosome condensation	3
mitotic sister chromatid segregation	2
mitotic cell cycle process	2
meiotic cell cycle	2
chromosome separation	2
positive regulation of cell cycle process	2
binding	2
chromosome	2
mitotic cell cycle	1
chromosome organization involved in meiotic cell cycle	1
T cell differentiation	1
female meiotic nuclear division	1
female meiosis chromosome segregation	1
meiotic chromosome separation	1
chromosome segregation	1
regulation of chromosome segregation	1
regulation of chromosome separation	1
regulation of chromosome condensation	1
positive regulation of chromosome organization	1
female gamete generation	1
meiotic nuclear division	1
chromosome organization	1
nuclear chromosome	1
condensed chromosome	1
nucleus	1
protein-containing complex	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
intracellular membraneless organelle	1

Protein interactions and networks

STRING

1212 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NCAPH2	NCAPG2	Q86XI2	999
NCAPH2	NCAPD3	P42695	997
NCAPH2	SMC4	Q9NTJ3	978
NCAPH2	NCAPD2	Q15021	938
NCAPH2	LPCAT3	Q6P1A2	796
NCAPH2	NCAPH	Q15003	777
NCAPH2	NCAPG	Q9BPX3	693
NCAPH2	LMF2	Q9BU23	668
NCAPH2	TERF1	P54274	612
NCAPH2	SMC2	O95347	592
NCAPH2	RAD21	O60216	570
NCAPH2	COASY	Q13057	508
NCAPH2	CD69	Q07108	468
NCAPH2	TNRC18	O15417	455
NCAPH2	OSBPL6	Q9BZF3	446

IntAct

78 interactions, top by confidence:

A	B	Type	Score
NCAPH2	SMC2	psi-mi:“MI:0915”(physical association)	0.720
NCAPH2	SMC2	psi-mi:“MI:0914”(association)	0.720
NCAPD3	NCAPH2	psi-mi:“MI:0915”(physical association)	0.720
NCAPH2	NCAPG2	psi-mi:“MI:0915”(physical association)	0.640
SDC2	PDPK1	psi-mi:“MI:0914”(association)	0.640
SMC4	NCAPH2	psi-mi:“MI:0915”(physical association)	0.640
BTN2	NCAPH2	psi-mi:“MI:0915”(physical association)	0.560
NCAPH2	BTN2	psi-mi:“MI:0915”(physical association)	0.560
PRPF31	NCAPH2	psi-mi:“MI:0915”(physical association)	0.560
FAM174A	BLTP3B	psi-mi:“MI:0914”(association)	0.530
CXCR4	TMEM120B	psi-mi:“MI:0914”(association)	0.530
CD226	MEN1	psi-mi:“MI:0914”(association)	0.530
CA14	EXOC5	psi-mi:“MI:0914”(association)	0.530
EPHA1	EXOC5	psi-mi:“MI:0914”(association)	0.530
WDR55	PES1	psi-mi:“MI:0914”(association)	0.530
RIC3	ATP9A	psi-mi:“MI:0914”(association)	0.530
HLA-B	LTN1	psi-mi:“MI:0914”(association)	0.530
WDR55	AP3D1	psi-mi:“MI:0914”(association)	0.530
SNAPC4	KDM5C	psi-mi:“MI:0914”(association)	0.530
DGCR2	HOXD13	psi-mi:“MI:0914”(association)	0.530
NCAPH2	EPRS1	psi-mi:“MI:0915”(physical association)	0.400
NCAPH2	PA	psi-mi:“MI:0915”(physical association)	0.370
NCAPH2	FOLR1	psi-mi:“MI:0915”(physical association)	0.370
NCAPH2	LMO2	psi-mi:“MI:0915”(physical association)	0.370

BioGRID (271): NCAPH2 (Two-hybrid), USHBP1 (Two-hybrid), EGLN3 (Two-hybrid), NCAPH2 (Affinity Capture-MS), NCAPH2 (Affinity Capture-MS), NCAPH2 (Affinity Capture-MS), NCAPH2 (Affinity Capture-MS), NCAPH2 (Affinity Capture-MS), NCAPH2 (Affinity Capture-MS), NCAPH2 (Affinity Capture-MS), NCAPH2 (Affinity Capture-MS), NCAPH2 (Affinity Capture-MS), NCAPH2 (Affinity Capture-MS), NCAPH2 (Affinity Capture-MS), NCAPH2 (Affinity Capture-MS)

ESM2 similar proteins: A2AU37, B2RYF7, B5DEB9, D2HSB3, D3ZND0, E1C760, E7EXT2, F7AEX0, O13067, O60566, O88665, Q05B18, Q0VBD2, Q0VC06, Q15003, Q28E45, Q28GV1, Q28IV8, Q32N92, Q3SZL8, Q4KLC4, Q4V8I2, Q564K3, Q5EAW4, Q5JTW2, Q5M985, Q5R789, Q5RH01, Q5RHY1, Q5ZKA6, Q641G4, Q68FR7, Q6IBW4, Q6NSQ7, Q6NTW1, Q6NU40, Q6NZY4, Q6TEL1, Q7L590, Q8BSP2

Diamond homologs: P34341, Q28GV1, Q3SZL8, Q641G4, Q6IBW4, Q8BSP2, Q4V8I2, Q5RH01, Q9LUR0

SIGNOR signaling

3 interactions.

A	Effect	B	Mechanism
NCAPH2	“form complex”	“Condensin II”	binding
NCAPH2	“up-regulates activity”	TERF1	binding
PLK1	“up-regulates activity”	NCAPH2	phosphorylation

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	21
Likely pathogenic	10
Uncertain significance	259
Likely benign	146
Benign	6

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1034155	NM_005138.3(SCO2):c.256C>T (p.Gln86Ter)	Pathogenic
2005691	NM_005138.3(SCO2):c.39del (p.Arg13fs)	Pathogenic
2130639	NM_005138.3(SCO2):c.544C>T (p.Gln182Ter)	Pathogenic
2703817	NM_005138.3(SCO2):c.169_191dup (p.Thr64_Gly65insPheGluProGlyCysTer)	Pathogenic
2721165	NM_005138.3(SCO2):c.74_81del (p.Thr25fs)	Pathogenic
2760098	NM_005138.3(SCO2):c.116C>A (p.Ser39Ter)	Pathogenic
2763900	NM_005138.3(SCO2):c.449dup (p.Leu151fs)	Pathogenic
2772673	NM_005138.3(SCO2):c.387_388del (p.Phe130fs)	Pathogenic
2776900	NM_005138.3(SCO2):c.121C>T (p.Gln41Ter)	Pathogenic
2779728	NM_005138.3(SCO2):c.445dup (p.Arg149fs)	Pathogenic
2783127	NM_005138.3(SCO2):c.539dup (p.Tyr180Ter)	Pathogenic
2798083	NM_005138.3(SCO2):c.108G>A (p.Trp36Ter)	Pathogenic
2800038	NM_005138.3(SCO2):c.330_331del (p.Gly111fs)	Pathogenic
2801894	NM_005138.3(SCO2):c.232_233del (p.Leu78fs)	Pathogenic
2829315	NM_005138.3(SCO2):c.438_439dup (p.Val147fs)	Pathogenic
2967556	NM_005138.3(SCO2):c.250_251del (p.Arg84fs)	Pathogenic
3013081	NM_005138.3(SCO2):c.358del (p.Arg120fs)	Pathogenic
5678	NM_005138.3(SCO2):c.157C>T (p.Gln53Ter)	Pathogenic
5679	NM_005138.3(SCO2):c.674C>T (p.Ser225Phe)	Pathogenic
5681	NM_005138.3(SCO2):c.418G>A (p.Glu140Lys)	Pathogenic
5685	NM_005138.3(SCO2):c.107G>A (p.Trp36Ter)	Pathogenic
2663033	NM_005138.3(SCO2):c.750_756dup (p.Ser253fs)	Likely pathogenic
2678605	NM_005138.3(SCO2):c.514_515dup (p.Asp172fs)	Likely pathogenic
2678606	NM_005138.3(SCO2):c.609_610del (p.His203fs)	Likely pathogenic
2678607	NM_005138.3(SCO2):c.672_682del (p.Ser225fs)	Likely pathogenic
2678608	NM_005138.3(SCO2):c.233_236delinsA (p.Leu78_Arg79delinsGln)	Likely pathogenic
3240427	NM_005138.3(SCO2):c.120_135del (p.Gly42fs)	Likely pathogenic
3588120	NM_005138.3(SCO2):c.508G>T (p.Glu170Ter)	Likely pathogenic
424006	NM_005138.3(SCO2):c.618dup (p.Val207fs)	Likely pathogenic
4820609	NM_005138.3(SCO2):c.540C>G (p.Tyr180Ter)	Likely pathogenic

SpliceAI

3510 predictions. Top by Δscore:

Variant	Effect	Δscore
22:50508442:GGAG:G	donor_gain	1.0000
22:50508443:GAGG:G	donor_gain	1.0000
22:50508444:AGG:A	donor_loss	1.0000
22:50508446:G:C	donor_loss	1.0000
22:50508447:T:G	donor_loss	1.0000
22:50516445:A:AG	acceptor_gain	1.0000
22:50516445:AGCT:A	acceptor_gain	1.0000
22:50516445:AGCTG:A	acceptor_gain	1.0000
22:50516446:G:GG	acceptor_gain	1.0000
22:50516446:GC:G	acceptor_gain	1.0000
22:50516446:GCT:G	acceptor_gain	1.0000
22:50516446:GCTG:G	acceptor_gain	1.0000
22:50516446:GCTGG:G	acceptor_gain	1.0000
22:50516541:G:GG	donor_gain	1.0000
22:50516545:GAAG:G	donor_gain	1.0000
22:50516547:AG:A	donor_loss	1.0000
22:50516548:GGTG:G	donor_loss	1.0000
22:50517479:AGAGG:A	donor_loss	1.0000
22:50517480:GAG:G	donor_gain	1.0000
22:50517481:AGGT:A	donor_loss	1.0000
22:50517483:GT:G	donor_loss	1.0000
22:50517575:AGGC:A	acceptor_gain	1.0000
22:50517576:GGCG:G	acceptor_gain	1.0000
22:50517662:G:GA	donor_loss	1.0000
22:50517662:G:GG	donor_gain	1.0000
22:50517739:A:AG	acceptor_gain	1.0000
22:50517740:G:GA	acceptor_gain	1.0000
22:50517808:GT:G	donor_gain	1.0000
22:50517810:G:GG	donor_gain	1.0000
22:50517927:T:A	acceptor_gain	1.0000

AlphaMissense

3978 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
22:50508401:T:A	W22R	0.999
22:50508401:T:C	W22R	0.999
22:50508403:G:C	W22C	0.999
22:50508403:G:T	W22C	0.999
22:50508381:T:A	I15N	0.998
22:50508384:G:C	R16P	0.998
22:50508390:T:C	L18P	0.998
22:50508426:T:C	L30P	0.998
22:50516495:T:C	F53L	0.998
22:50516497:C:A	F53L	0.998
22:50516497:C:G	F53L	0.998
22:50516504:G:C	A56P	0.998
22:50516507:G:C	A57P	0.998
22:50516517:T:A	I60N	0.998
22:50516529:C:A	A64D	0.998
22:50517437:T:C	L74P	0.998
22:50508402:G:C	W22S	0.997
22:50516496:T:C	F53S	0.997
22:50516508:C:A	A57E	0.997
22:50516517:T:G	I60S	0.997
22:50508381:T:G	I15S	0.996
22:50508438:T:C	L34P	0.996
22:50516525:T:C	S63P	0.996
22:50516535:T:A	V66D	0.996
22:50516537:T:C	Y67H	0.996
22:50516537:T:G	Y67D	0.996
22:50516540:A:C	S68R	0.996
22:50516542:T:A	S68R	0.996
22:50516542:T:G	S68R	0.996
22:50517446:T:C	L77P	0.996

dbSNP variants (sampled 300 via entrez): RS1000069929 (22:50524727 C>G), RS1000126184 (22:50521384 T>C,G), RS1000222846 (22:50521202 C>T), RS1000482004 (22:50508098 C>CA,CT), RS1000658598 (22:50511950 G>A,T), RS1000746508 (22:50516837 C>A,G), RS1000906384 (22:50507287 G>A,C,T), RS1000981626 (22:50513719 G>A), RS1001011060 (22:50520533 C>G,T), RS1001040813 (22:50520725 A>G), RS1001088754 (22:50508334 G>A,T), RS1001154865 (22:50520943 G>A,C), RS1001282508 (22:50514556 A>G), RS1001294311 (22:50508204 G>A,C), RS1001315003 (22:50514747 T>C)

Disease associations

OMIM: gene MIM:611230 | disease phenotypes: MIM:604377, MIM:608908, MIM:220110, MIM:603041, MIM:118450

GenCC curated gene-disease

Mondo (5): cardioencephalomyopathy, fatal infantile, due to cytochrome c oxidase deficiency 1 (MONDO:0011451), myopia 6 (MONDO:0012154), mitochondrial complex IV deficiency, nuclear type 1 (MONDO:0700250), mitochondrial DNA depletion syndrome 1 (MONDO:0011283), Alagille syndrome due to a JAG1 point mutation (MONDO:0016862)

Orphanet (4): Fatal infantile cytochrome C oxidase deficiency (Orphanet:1561), Mitochondrial neurogastrointestinal encephalomyopathy (Orphanet:298), Alagille syndrome due to a JAG1 point mutation (Orphanet:261619), Alagille syndrome (Orphanet:52)

HPO phenotypes

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

GWAS associations

10 associations (top):

Study	Trait	p-value
GCST000587_8	Mean corpuscular hemoglobin	4.000000e-08
GCST001765_31	Red blood cell traits	5.000000e-23
GCST003134_22	Cerebrospinal fluid clusterin levels	9.000000e-06
GCST004099_18	B-cell malignancies (chronic lymphocytic leukemia, Hodgkin lymphoma or multiple myeloma) (pleiotropy)	7.000000e-08
GCST004146_29	Chronic lymphocytic leukemia	3.000000e-09
GCST012020_514	Serum metabolite levels	1.000000e-27
GCST90002390_284	Mean corpuscular hemoglobin	4.000000e-10
GCST90002392_230	Mean corpuscular volume	4.000000e-16
GCST90002396_94	Mean reticulocyte volume	6.000000e-34
GCST90002397_612	Mean spheric corpuscular volume	4.000000e-22

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0004509	hemoglobin measurement
EFO:0004527	mean corpuscular hemoglobin
EFO:0010701	mean reticulocyte volume

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C536105	Myopia 6 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	increases methylation, increases expression, affects cotreatment	2
sodium arsenite	decreases expression, increases expression	2
Valproic Acid	affects expression, increases methylation	2
FR900359	decreases phosphorylation	1
triphenyl phosphate	affects expression	1
beta-lapachone	decreases expression	1
butyraldehyde	increases expression	1
zinc chromate	decreases expression, increases abundance	1
coumarin	affects phosphorylation	1
chromium hexavalent ion	increases abundance, decreases expression	1
abrine	increases expression	1
Fulvestrant	affects cotreatment, increases methylation	1
Acetaminophen	increases expression	1
Air Pollutants	affects expression, increases abundance	1
Atrazine	decreases expression	1
Vehicle Emissions	increases abundance, decreases expression	1
Benzo(a)pyrene	increases methylation	1
Cisplatin	increases expression	1
Coumestrol	increases expression	1
Dichlorodiphenyl Dichloroethylene	increases expression	1
Ivermectin	decreases expression	1
Methyl Methanesulfonate	increases expression	1
Nickel	increases expression	1
Ozone	affects expression, increases abundance	1
Quercetin	decreases phosphorylation	1
Smoke	decreases expression	1
Tetrachlorodibenzodioxin	affects expression	1
Tobacco Smoke Pollution	increases expression	1
Tretinoin	decreases expression	1
Particulate Matter	decreases expression, increases abundance	1

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_1D64	HeLa Kyoto EGFP-Kleisin-beta	Cancer cell line	Female

Clinical trials (associated diseases)

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