NCAPD2

Summary

NCAPD2 (non-SMC condensin I complex subunit D2, HGNC:24305) is a protein-coding gene on chromosome 12p13.31, encoding Condensin complex subunit 1 (Q15021). Regulatory subunit of the condensin complex, a complex required for conversion of interphase chromatin into mitotic-like condense chromosomes. It is a common-essential gene (DepMap: required in 99.3% of cancer cell lines).

Enables histone binding activity. Involved in mitotic chromosome condensation and positive regulation of chromosome condensation. Located in several cellular components, including condensed chromosome; microtubule organizing center; and nuclear lumen. Part of condensin complex. Implicated in primary autosomal recessive microcephaly 21.

Source: NCBI Gene 9918 — RefSeq curated summary.

At a glance

• Gene–disease (curated): microcephaly 21, primary, autosomal recessive (Strong, GenCC)
• Clinical variants (ClinVar): 330 total — 2 pathogenic, 6 likely-pathogenic
• Phenotypes (HPO): 9
• Druggable target: yes
• Cancer dependency (DepMap): dependent in 99.3% of screened cell lines (common-essential)
• MANE Select transcript: NM_014865

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:24305
Approved symbol	NCAPD2
Name	non-SMC condensin I complex subunit D2
Location	12p13.31
Locus type	gene with protein product
Status	Approved
Aliases	CNAP1, hCAP-D2, CAP-D2, KIAA0159
Ensembl gene	ENSG00000010292
Ensembl biotype	protein_coding
OMIM	615638
Entrez	9918

Gene structure

Transcript identifiers

Ensembl transcripts: 21 — 11 protein_coding, 8 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay, 1 retained_intron

ENST00000315579, ENST00000382457, ENST00000535804, ENST00000536090, ENST00000536538, ENST00000538600, ENST00000539084, ENST00000539714, ENST00000539885, ENST00000541399, ENST00000542472, ENST00000542492, ENST00000545732, ENST00000925383, ENST00000925384, ENST00000925385, ENST00000925386, ENST00000925387, ENST00000925388, ENST00000925389, ENST00000925390

RefSeq mRNA: 1 — MANE Select: NM_014865 NM_014865

CCDS: CCDS8548

Canonical transcript exons

ENST00000315579 — 32 exons

Exon	Start	End
ENSE00001296138	6531327	6531955
ENSE00001309685	6494102	6494154
ENSE00003471783	6517779	6517959
ENSE00003472819	6510629	6510810
ENSE00003492857	6522828	6523002
ENSE00003493403	6529775	6529958
ENSE00003494198	6521798	6522037
ENSE00003500696	6525583	6525716
ENSE00003502347	6514773	6514920
ENSE00003508626	6495076	6495225
ENSE00003514214	6528173	6528328
ENSE00003516830	6528945	6529039
ENSE00003518940	6523262	6523346
ENSE00003546109	6509717	6509792
ENSE00003549100	6528679	6528856
ENSE00003550385	6530691	6530817
ENSE00003554872	6510075	6510133
ENSE00003577073	6517365	6517499
ENSE00003582090	6530921	6531076
ENSE00003582871	6526068	6526200
ENSE00003583422	6529513	6529593
ENSE00003605109	6516828	6517025
ENSE00003610442	6514464	6514587
ENSE00003618388	6511110	6511252
ENSE00003627001	6517596	6517683
ENSE00003660345	6526287	6526371
ENSE00003670899	6526891	6527063
ENSE00003673412	6514265	6514392
ENSE00003678391	6526448	6526615
ENSE00003687839	6520986	6521110
ENSE00003688725	6527777	6527888
ENSE00003789318	6527968	6528091

Expression profiles

Bgee: expression breadth ubiquitous, 215 present calls, max score 97.89.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 38.7340 / max 507.5059, expressed in 1802 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
123681	25.8064	1630
123679	8.7944	1768
123680	4.0661	1088
123683	0.0671	26

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
ventricular zone	UBERON:0003053	97.89	gold quality
ganglionic eminence	UBERON:0004023	95.71	gold quality
bone marrow cell	CL:0002092	92.93	gold quality
embryo	UBERON:0000922	92.88	gold quality
stromal cell of endometrium	CL:0002255	91.94	gold quality
granulocyte	CL:0000094	91.64	gold quality
endometrium epithelium	UBERON:0004811	89.74	gold quality
rectum	UBERON:0001052	89.08	gold quality
colonic epithelium	UBERON:0000397	88.98	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	88.27	gold quality
descending thoracic aorta	UBERON:0002345	87.92	gold quality
mucosa of stomach	UBERON:0001199	87.82	gold quality
leukocyte	CL:0000738	87.74	gold quality
esophagus mucosa	UBERON:0002469	87.71	gold quality
mucosa of transverse colon	UBERON:0004991	87.54	gold quality
monocyte	CL:0000576	87.53	gold quality
vermiform appendix	UBERON:0001154	87.48	gold quality
sural nerve	UBERON:0015488	87.48	gold quality
adrenal tissue	UBERON:0018303	87.38	gold quality
mononuclear cell	CL:0000842	87.31	gold quality
lymph node	UBERON:0000029	87.29	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	87.22	gold quality
lower esophagus mucosa	UBERON:0035834	87.17	gold quality
right testis	UBERON:0004534	87.13	gold quality
left testis	UBERON:0004533	87.01	gold quality
thoracic aorta	UBERON:0001515	86.61	gold quality
small intestine Peyer’s patch	UBERON:0003454	86.58	gold quality
ascending aorta	UBERON:0001496	86.50	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	86.43	gold quality
tonsil	UBERON:0002372	86.35	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-CURD-112	yes	13.49
E-MTAB-6678	yes	8.64
E-ANND-3	yes	7.39
E-GEOD-99795	no	432.29

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

35 targeting NCAPD2, 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-3162-3P	100.00	65.37	363
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-548AE-3P	99.93	72.66	4867
HSA-MIR-548AH-3P	99.93	72.54	4872
HSA-MIR-548AM-3P	99.93	72.54	4872
HSA-MIR-548AQ-3P	99.93	72.66	4867
HSA-MIR-182-5P	99.87	74.03	2589
HSA-MIR-548D-3P	99.87	70.67	4362
HSA-MIR-548BB-3P	99.86	70.58	4354
HSA-MIR-548AC	99.84	70.77	4351
HSA-MIR-548H-3P	99.84	70.80	4349
HSA-MIR-548Z	99.84	70.80	4349
HSA-MIR-4524A-3P	99.72	66.85	2406
HSA-MIR-4729	99.69	72.18	4233
HSA-MIR-4470	99.66	69.35	1767
HSA-MIR-7106-5P	99.53	67.47	3574
HSA-MIR-12123	99.52	71.79	2990
HSA-MIR-4735-5P	99.43	68.49	1780
HSA-MIR-1276	99.36	68.18	1642
HSA-MIR-504-3P	99.30	67.18	1745
HSA-MIR-664A-3P	99.22	71.08	2696
HSA-MIR-548L	99.06	70.90	2560
HSA-MIR-7151-3P	99.04	69.72	2370
HSA-MIR-6074	98.89	69.64	2187
HSA-MIR-619-5P	98.57	64.97	1988
HSA-MIR-6841-3P	98.08	66.54	604

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 99.3% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 11)

• Data show the CNAP1 C-terminal region defines a novel histone-binding domain that is responsible for targeting CNAP1, and possibly condensin, to mitotic chromosomes. (PMID:12138188)
• Data show that that DNA repear process is dictated by PARP1 through its interaction with the chromosome-targeting domain of the hCAP-D2 subunit of condensin I. (PMID:21858164)
• Study has shown that both rs7311174 and rs2072374 in the NCAPD2 gene are associated with Parkinson’s disease in a Han Chinese population. (PMID:25166511)
• The authors propose that histone H3 threonine 118 phosphorylation via Aurora-A alters the chromatin structure during specific phases of mitosis to promote timely condensin I and cohesin disassociation, which is essential for effective chromosome segregation. (PMID:26878753)
• this is the second report of primary microcephaly due to a pathogenic variant at the NCAPD2 gene. We found two affected siblings who carried a splice-site pathogenic variant (c.3477+2T>C). Our finding provided accurate diagnosis and genetic counseling to the family. (PMID:31056748)
• High NCAPD2 expression was associated with lymph node metastasis in Triple-Negative Breast Cancer. (PMID:31610177)
• NCAPD2 and NCAPD3 expression levels have been confirmed to be significantly up-regulated in the intestinal mucosa of patients with active ulcerative colitis. In vitro, the data suggested that silencing NACPD2 and NACPD3 could depress the expression of IL-1beta, IL-6 and TNF-alpha. Further, knockdown of NACPD2 and NACPD3 could remarkably suppress IKK nucleation and NF-kappaB volume. (PMID:31885422)
• NCAPD2 inhibits autophagy by regulating Ca(2+)/CAMKK2/AMPK/mTORC1 pathway and PARP-1/SIRT1 axis to promote colorectal cancer. (PMID:34229059)
• NCAPD2 promotes breast cancer progression through E2F1 transcriptional regulation of CDK1. (PMID:35348268)
• NCAPD2 is a novel marker for the poor prognosis of lung adenocarcinoma and is associated with immune infiltration and tumor mutational burden. (PMID:36701707)
• Non-SMC condensin I complex subunit D2 (NCAPD2) reveals its prognostic and immunologic features in human cancers. (PMID:37498296)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	ncapd2	ENSDARG00000005058
mus_musculus	Ncapd2	ENSMUSG00000038252
rattus_norvegicus	Ncapd2	ENSRNOG00000055300
drosophila_melanogaster	Cap-D2	FBGN0039680

Paralogs (1): NCAPD3 (ENSG00000151503)

Protein

Protein identifiers

Condensin complex subunit 1 — Q15021 (reviewed: Q15021)

Alternative names: Chromosome condensation-related SMC-associated protein 1, Chromosome-associated protein D2, Non-SMC condensin I complex subunit D2, XCAP-D2 homolog

All UniProt accessions (4): Q15021, E7EN77, F5GZK7, F5H431

UniProt curated annotations — full annotation on UniProt →

Function. Regulatory subunit of the condensin complex, a complex required for conversion of interphase chromatin into mitotic-like condense chromosomes. The condensin complex probably introduces positive supercoils into relaxed DNA in the presence of type I topoisomerases and converts nicked DNA into positive knotted forms in the presence of type II topoisomerases. May target the condensin complex to DNA via its C-terminal domain. 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 non-centromeric ultrafine DNA bridges during 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.

Subunit / interactions. Component of the condensin complex, which contains the SMC2 and SMC4 heterodimer, and three non SMC subunits that probably regulate the complex: NCAPH/BRRN1, NCAPD2/CAPD2 and NCAPG. Interacts with histones H1 and H3.

Subcellular location. Nucleus. Cytoplasm. Chromosome.

Post-translational modifications. Phosphorylated by CDK1. Its phosphorylation, as well as that of NCAPH and NCAPG subunits, activates the condensin complex and is required for chromosome condensation.

Disease relevance. Microcephaly 21, primary, autosomal recessive (MCPH21) [MIM:617983] A form of microcephaly, a disease defined as a head circumference more than 3 standard deviations below the age, sex and ethnically matched mean. Brain weight is markedly reduced and the cerebral cortex is disproportionately small. MCPH21 features include mild intellectual disability, intrauterine growth retardation, short stature, and microcephaly. The disease is caused by variants affecting the gene represented in this entry.

Domain organisation. The C-terminal domain interacts with histones H1 and H3, and may be responsible for condensin complex targeting to mitotic chromosomes. This domain is independent from the bipartite nuclear localization signal, although they are contained within the same region.

Similarity. Belongs to the CND1 (condensin subunit 1) family.

RefSeq proteins (1): NP_055680* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR007673	Condensin_cplx_su1	Family
IPR011989	ARM-like	Homologous_superfamily
IPR016024	ARM-type_fold	Homologous_superfamily
IPR024324	Condensin_cplx_su1_N	Domain
IPR026971	CND1/NCAPD3	Family
IPR032682	Cnd1_C	Domain

Pfam: PF12717, PF12922

UniProt features (36 total): modified residue 16, compositionally biased region 5, sequence variant 5, region of interest 4, mutagenesis site 2, sequence conflict 2, chain 1, short sequence motif 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q15021-F1	79.94	0.41

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 (16): 20, 585, 1310, 1315, 1330, 1331, 1333, 1339, 1366, 1367, 1370, 1371, 1376, 1384, 1389, 1395

Mutagenesis-validated functional residues (2):

Position	Phenotype
1343–1348	abolishes localization to the nucleus, while it only reduces chromosome binding.
1358–1360	abolishes localization to the nucleus, while it only reduces chromosome binding.

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-2514853	Condensation of Prometaphase Chromosomes

MSigDB gene sets: 302 (showing top): GNF2_CKS1B, GOBP_CHROMOSOME_ORGANIZATION, HORIUCHI_WTAP_TARGETS_DN, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, MITSIADES_RESPONSE_TO_APLIDIN_DN, GOBP_CHROMOSOME_SEPARATION, GOBP_POSITIVE_REGULATION_OF_ORGANELLE_ORGANIZATION, KONG_E2F3_TARGETS, GOBP_CHROMOSOME_CONDENSATION, PUJANA_CHEK2_PCC_NETWORK, MODULE_118, MARTINEZ_RB1_TARGETS_UP, GOBP_ORGANELLE_FISSION, GOBP_REGULATION_OF_CHROMOSOME_SEGREGATION, BLALOCK_ALZHEIMERS_DISEASE_UP

GO Biological Process (8): mitotic chromosome condensation (GO:0007076), meiotic chromosome condensation (GO:0010032), cell division (GO:0051301), positive regulation of chromosome segregation (GO:0051984), positive regulation of chromosome separation (GO:1905820), positive regulation of chromosome condensation (GO:1905821), mitotic cell cycle (GO:0000278), chromosome condensation (GO:0030261)

GO Molecular Function (2): histone binding (GO:0042393), protein binding (GO:0005515)

GO Cellular Component (13): condensed chromosome, centromeric region (GO:0000779), condensed chromosome (GO:0000793), condensed nuclear chromosome (GO:0000794), condensin complex (GO:0000796), nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), cytosol (GO:0005829), membrane (GO:0016020), centriolar satellite (GO:0034451), ciliary basal body (GO:0036064), nuclear chromosome (GO:0000228), chromosome (GO:0005694)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Mitotic Prometaphase	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	5
chromosome condensation	3
chromosome	3
positive regulation of cell cycle process	2
condensed chromosome	2
nucleus	2
nuclear lumen	2
mitotic sister chromatid segregation	1
mitotic cell cycle	1
mitotic cell cycle process	1
meiotic cell cycle	1
chromosome organization involved in meiotic cell cycle	1
cellular process	1
chromosome segregation	1
regulation of chromosome segregation	1
chromosome separation	1
regulation of chromosome separation	1
regulation of chromosome condensation	1
positive regulation of chromosome organization	1
cell cycle	1
mitotic nuclear division	1
chromosome organization	1
protein binding	1
binding	1
chromosome, centromeric region	1
nuclear chromosome	1
protein-containing complex	1
intracellular membrane-bounded organelle	1
intracellular anatomical structure	1
cytoplasm	1
centrosome	1
microtubule organizing center	1
cilium	1
intracellular membraneless organelle	1

Protein interactions and networks

STRING

2118 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NCAPD2	NCAPH	Q15003	998
NCAPD2	SMC4	Q9NTJ3	998
NCAPD2	NCAPG	Q9BPX3	995
NCAPD2	SMC2	O95347	965
NCAPD2	NCAPG2	Q86XI2	939
NCAPD2	NCAPH2	Q6IBW4	938
NCAPD2	RAD21	O60216	795
NCAPD2	NCAPD3	P42695	768
NCAPD2	SMC3	Q9UQE7	627
NCAPD2	SMC5	Q8IY18	593
NCAPD2	GAS2L3	Q86XJ1	572
NCAPD2	ESPL1	Q14674	549
NCAPD2	POLA1	P09884	524
NCAPD2	AURKB	Q96GD4	517
NCAPD2	G2E3	Q7L622	498

IntAct

129 interactions, top by confidence:

A	B	Type	Score
ARPC1A	ARPC2	psi-mi:“MI:0914”(association)	0.900
NCAPH	SMC2	psi-mi:“MI:0915”(physical association)	0.810
RFXANK	RFXAP	psi-mi:“MI:0914”(association)	0.780
CDK19	MED19	psi-mi:“MI:0914”(association)	0.770
NCAPH	NCAPD2	psi-mi:“MI:0915”(physical association)	0.720
NCAPD2	NCAPH	psi-mi:“MI:0915”(physical association)	0.720
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
NCAPG	NCAPD2	psi-mi:“MI:0915”(physical association)	0.560
SNRNP27	UBA6	psi-mi:“MI:0914”(association)	0.530
HTR2C	KLRG2	psi-mi:“MI:0914”(association)	0.530
MAS1	POTEF	psi-mi:“MI:0914”(association)	0.530
FCGRT	GOLIM4	psi-mi:“MI:0914”(association)	0.530
FZD10	NRP1	psi-mi:“MI:0914”(association)	0.530
BMP1	TLL1	psi-mi:“MI:0914”(association)	0.530
CXCR4	TMEM120B	psi-mi:“MI:0914”(association)	0.530
DPEP1	ILVBL	psi-mi:“MI:0914”(association)	0.530
GPR137B	DOC2A	psi-mi:“MI:0914”(association)	0.530

BioGRID (306): NCAPD2 (Affinity Capture-MS), NCAPD2 (Affinity Capture-MS), NCAPD2 (Affinity Capture-MS), NCAPD2 (Affinity Capture-MS), NCAPD2 (Affinity Capture-MS), NCAPD2 (Co-fractionation), NCAPG (Co-fractionation), NCAPH (Co-fractionation), SMC2 (Co-fractionation), SMC4 (Co-fractionation), NCAPD2 (Affinity Capture-MS), NCAPD2 (Synthetic Lethality), NCAPD2 (Proximity Label-MS), NCAPD2 (Affinity Capture-MS), NCAPD2 (Affinity Capture-MS)

ESM2 similar proteins: A0A1S4D1D3, A0A1W2PR95, A0A8I6ASZ5, A8WE67, D2K8N5, D3Z8X7, D3ZND0, E1C760, E7EXT2, F6Y9J3, F7AEX0, O08836, O60308, P27641, P54729, P78318, Q0P4W3, Q14CX7, Q15021, Q2QY04, Q2YD98, Q3ZC62, Q4V8E4, Q5EAU9, Q61249, Q68FJ0, Q6NY52, Q6PBQ2, Q6PGY6, Q6QI44, Q7ZXA8, Q80V31, Q86VS3, Q8BWZ3, Q8C6E0, Q8C9J3, Q8IYW2, Q8K2Z4, Q8LDQ4, Q8LNU5

Diamond homologs: Q15021, Q6ZQK0, Q8K2Z4, Q9YHY6, P42695, Q6GN08

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
NCAPD2	“form complex”	“Condensin I”	binding
NEK2	“down-regulates activity”	NCAPD2	phosphorylation

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	2
Likely pathogenic	6
Uncertain significance	229
Likely benign	37
Benign	20

Top pathogenic / likely-pathogenic (8)

Variant ID	HGVS	Classification
1711943	NM_014865.4(NCAPD2):c.3964+2T>C	Pathogenic
441823	GRCh37/hg19 12p13.33-13.2(chr12:173786-11677456)x3	Pathogenic
1339659	NM_014865.4(NCAPD2):c.2508del (p.Phe837fs)	Likely pathogenic
2663273	NM_014865.4(NCAPD2):c.1150_1151del (p.Val384fs)	Likely pathogenic
3780009	NM_014865.4(NCAPD2):c.806_807del (p.Tyr269fs)	Likely pathogenic
4849400	NM_014865.4(NCAPD2):c.532C>T (p.Gln178Ter)	Likely pathogenic
4849449	NM_014865.4(NCAPD2):c.2761_2777delinsG (p.Phe921fs)	Likely pathogenic
546695	NM_014865.4(NCAPD2):c.445-1G>T	Likely pathogenic

SpliceAI

4876 predictions. Top by Δscore:

Variant	Effect	Δscore
12:6493362:T:TA	donor_gain	1.0000
12:6509790:GCA:G	donor_gain	1.0000
12:6509793:G:GG	donor_gain	1.0000
12:6510625:ACAGT:A	acceptor_gain	1.0000
12:6510627:A:AG	acceptor_gain	1.0000
12:6510627:AGT:A	acceptor_gain	1.0000
12:6510627:AGTG:A	acceptor_gain	1.0000
12:6510628:G:GG	acceptor_gain	1.0000
12:6510628:GT:G	acceptor_gain	1.0000
12:6510628:GTG:G	acceptor_gain	1.0000
12:6510628:GTGG:G	acceptor_gain	1.0000
12:6510628:GTGGT:G	acceptor_gain	1.0000
12:6510804:TGGGA:T	donor_gain	1.0000
12:6510808:A:T	donor_gain	1.0000
12:6510808:AAGG:A	donor_loss	1.0000
12:6510812:T:A	donor_loss	1.0000
12:6511087:A:AG	acceptor_gain	1.0000
12:6511089:T:G	acceptor_gain	1.0000
12:6511094:ACAT:A	acceptor_gain	1.0000
12:6511096:AT:A	acceptor_gain	1.0000
12:6511097:T:G	acceptor_gain	1.0000
12:6511097:T:TA	acceptor_gain	1.0000
12:6511108:AG:A	acceptor_gain	1.0000
12:6511109:GG:G	acceptor_gain	1.0000
12:6511250:CAGG:C	donor_loss	1.0000
12:6511251:AGG:A	donor_loss	1.0000
12:6511252:GG:G	donor_loss	1.0000
12:6511253:GT:G	donor_loss	1.0000
12:6511254:T:A	donor_loss	1.0000
12:6514263:A:AG	acceptor_gain	1.0000

AlphaMissense

9155 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:6528735:T:C	L1119P	0.998
12:6528846:T:C	L1156P	0.997
12:6528274:T:C	L1082P	0.996
12:6528967:T:C	L1167P	0.996
12:6528741:T:C	L1121P	0.995
12:6528757:G:C	K1126N	0.995
12:6528757:G:T	K1126N	0.995
12:6528782:G:C	A1135P	0.995
12:6528964:T:C	L1166P	0.995
12:6528988:T:C	L1174P	0.995
12:6529557:T:C	L1206P	0.995
12:6528681:T:A	L1101H	0.994
12:6528755:A:G	K1126E	0.994
12:6528783:C:A	A1135E	0.994
12:6528962:T:A	N1165K	0.994
12:6528962:T:G	N1165K	0.994
12:6529569:T:C	L1210P	0.994
12:6495120:T:C	F8L	0.993
12:6495122:C:A	F8L	0.993
12:6495122:C:G	F8L	0.993
12:6509782:A:C	S65R	0.993
12:6509784:C:A	S65R	0.993
12:6509784:C:G	S65R	0.993
12:6528681:T:C	L1101P	0.993
12:6528773:A:C	S1132R	0.993
12:6528775:C:A	S1132R	0.993
12:6528775:C:G	S1132R	0.993
12:6528957:T:G	Y1164D	0.993
12:6529518:T:C	L1193P	0.993
12:6529565:A:G	K1209E	0.993

dbSNP variants (sampled 300 via entrez): RS1000011590 (12:6508619 T>C), RS1000212226 (12:6512870 A>G), RS1000499384 (12:6513067 A>G,T), RS1000611634 (12:6503864 A>C), RS1000795760 (12:6521252 G>A,T), RS1000859712 (12:6520489 C>G), RS1000859870 (12:6525715 C>T), RS1000872156 (12:6516048 T>C), RS1000920332 (12:6520207 T>C), RS1001100310 (12:6531752 C>T), RS1001125 (12:6492808 T>C), RS1001126 (12:6492736 A>G), RS1001127 (12:6492577 A>C,T), RS1001176277 (12:6520060 A>G), RS1001265519 (12:6532043 G>A)

Disease associations

OMIM: gene MIM:615638 | disease phenotypes: MIM:617983

GenCC curated gene-disease

Disease	Classification	Inheritance
microcephaly 21, primary, autosomal recessive	Strong	Autosomal recessive

Mondo (1): microcephaly 21, primary, autosomal recessive (MONDO:0054804)

Orphanet (0):

HPO phenotypes

9 total (9 of 9 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000340	Sloping forehead
HP:0000729	Autistic behavior
HP:0001344	Absent speech
HP:0001518	Small for gestational age
HP:0002342	Moderate intellectual disability
HP:0003577	Congenital onset
HP:0004322	Short stature
HP:0011451	Primary microcephaly

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6067381 (SINGLE PROTEIN)

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

ChEMBL bioactivities

2 potent at pChembl≥5 of 2 total, top 2 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.54	Kd	28.75	nM	CHEMBL5653589
7.54	ED50	28.75	nM	CHEMBL5653589

PubChem BioAssay actives

1 with measured affinity, of 2 total; 1 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
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148828: Binding affinity to human NCAPD2 incubated for 45 mins by Kinobead based pull down assay	kd	0.0288	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	affects expression, decreases expression, increases expression	3
sodium arsenite	decreases expression, affects cotreatment, increases abundance, increases expression	3
Air Pollutants	affects cotreatment, increases abundance, increases oxidation, decreases expression	3
Cyclosporine	decreases expression	3
Cadmium Chloride	affects expression, decreases expression, increases expression	3
trichostatin A	affects cotreatment, decreases expression	2
Acetaminophen	decreases expression, increases expression	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
Tobacco Smoke Pollution	decreases expression	2
Valproic Acid	decreases expression, decreases methylation	2
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	2
Particulate Matter	increases abundance, affects cotreatment, decreases expression	2
FR900359	affects phosphorylation	1
dicrotophos	increases expression	1
chloroacetaldehyde	affects expression	1
triphenyl phosphate	affects expression	1
alpha-pinene	affects cotreatment, increases oxidation, increases abundance	1
propionaldehyde	decreases expression	1
arsenite	affects binding, decreases reaction	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
cobaltous chloride	decreases expression	1
perfluorooctanoic acid	decreases expression	1
zinc chromate	decreases expression, increases abundance	1
manganese chloride	affects cotreatment, decreases expression, increases abundance	1
coumarin	increases phosphorylation	1
cupric oxide	decreases expression	1
methacrylaldehyde	increases oxidation, increases abundance, affects cotreatment	1
isobutyl alcohol	affects cotreatment, decreases expression, increases abundance	1
diallyl trisulfide	decreases expression	1
di-n-butylphosphoric acid	affects expression	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5651870	Binding	Binding affinity to human NCAPD2 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 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_1D60	HeLa Kyoto EGFP-Cap-D2	Cancer cell line	Female

Clinical trials (associated diseases)

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