HMCN2

Summary

HMCN2 (hemicentin 2, HGNC:21293) is a protein-coding gene on chromosome 9q34.11, encoding Hemicentin-2 (Q8NDA2).

Predicted to enable axon guidance receptor activity. Predicted to be involved in homophilic cell adhesion via plasma membrane adhesion molecules and synapse organization. Located in collagen-containing extracellular matrix.

Source: NCBI Gene 256158 — RefSeq curated summary.

At a glance

• GWAS associations: 4
• Clinical variants (ClinVar): 35 total
• MANE Select transcript: NM_001291815

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:21293
Approved symbol	HMCN2
Name	hemicentin 2
Location	9q34.11
Locus type	gene with protein product
Status	Approved
Aliases	DKFZp434P0216, FLJ23816
Ensembl gene	ENSG00000148357
Ensembl biotype	protein_coding
OMIM	621107
Entrez	256158

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 4 protein_coding, 2 retained_intron, 1 nonsense_mediated_decay

ENST00000428715, ENST00000480829, ENST00000487727, ENST00000611173, ENST00000623487, ENST00000624552, ENST00000683500

RefSeq mRNA: 1 — MANE Select: NM_001291815 NM_001291815

CCDS: CCDS94512

Canonical transcript exons

ENST00000683500 — 98 exons

Exon	Start	End
ENSE00000984678	130432429	130432555
ENSE00001110474	130431367	130431486
ENSE00001595429	130433348	130434123
ENSE00001597348	130356088	130356257
ENSE00001600750	130430284	130430604
ENSE00001605965	130427313	130427375
ENSE00001607288	130354763	130355044
ENSE00001612229	130294855	130295026
ENSE00001616719	130286188	130286310
ENSE00001617437	130296674	130296794
ENSE00001625829	130299025	130299288
ENSE00001644680	130357834	130357988
ENSE00001645318	130309912	130310061
ENSE00001645518	130359319	130359414
ENSE00001654315	130304730	130305002
ENSE00001655564	130307453	130307566
ENSE00001658117	130429557	130429685
ENSE00001659180	130358390	130358486
ENSE00001668741	130348545	130348675
ENSE00001690775	130351423	130351577
ENSE00001697266	130285158	130285316
ENSE00001700226	130425687	130425924
ENSE00001705614	130348984	130349131
ENSE00001713403	130302857	130303001
ENSE00001715350	130428358	130428489
ENSE00001720314	130418772	130419041
ENSE00001725516	130352927	130353205
ENSE00001729778	130355746	130355854
ENSE00001741630	130306811	130306938
ENSE00001747889	130349537	130349663
ENSE00001755203	130424776	130424913
ENSE00001779276	130425009	130425130
ENSE00001783839	130303487	130303608
ENSE00001785273	130284603	130284673
ENSE00001785355	130427497	130427619
ENSE00001797490	130360428	130360604
ENSE00001798131	130422577	130422726
ENSE00001798368	130410571	130410652
ENSE00001801119	130306129	130306270
ENSE00001801747	130295666	130295772
ENSE00001817670	130373038	130373124
ENSE00001846860	130391935	130392118
ENSE00001860527	130372294	130372407
ENSE00001868878	130391450	130391574
ENSE00001882454	130390977	130391120
ENSE00001884742	130391204	130391363
ENSE00001911097	130388409	130388540
ENSE00001925763	130386443	130386524
ENSE00003621372	130384685	130384798
ENSE00003627423	130385560	130385762
ENSE00003639979	130384373	130384534
ENSE00003732886	130325811	130325970
ENSE00003736411	130319495	130319695
ENSE00003737168	130320356	130320451
ENSE00003739522	130327310	130327475
ENSE00003747723	130325595	130325707
ENSE00003751353	130320776	130320903
ENSE00003754676	130321787	130321931
ENSE00003755059	130362867	130362990
ENSE00003755188	130375876	130375989
ENSE00003755309	130394385	130394575
ENSE00003755472	130347166	130347360
ENSE00003755732	130405955	130406168
ENSE00003755851	130377649	130377799
ENSE00003755948	130399511	130399632
ENSE00003756045	130403741	130403875
ENSE00003756245	130341111	130341365
ENSE00003756283	130364714	130364889
ENSE00003756362	130370964	130371131
ENSE00003756447	130397528	130397655
ENSE00003756682	130369570	130369851
ENSE00003757125	130407571	130407705
ENSE00003757791	130365876	130365995
ENSE00003758080	130382679	130382866
ENSE00003758200	130337894	130338021
ENSE00003758280	130362008	130362165
ENSE00003758382	130376516	130376658
ENSE00003758566	130374502	130374693
ENSE00003758579	130403194	130403328
ENSE00003758798	130342350	130342436
ENSE00003758799	130402789	130402896
ENSE00003759024	130383504	130383600
ENSE00003759183	130400783	130400947
ENSE00003759221	130382184	130382297
ENSE00003759268	130404869	130405059
ENSE00003759317	130408743	130408933
ENSE00003759411	130393212	130393309
ENSE00003759501	130393742	130394008
ENSE00003759519	130396169	130396313
ENSE00003759634	130395924	130396065
ENSE00003759746	130395027	130395108
ENSE00003759778	130365631	130365727
ENSE00003759898	130375563	130375736
ENSE00003760209	130368276	130368437
ENSE00003760215	130379249	130379467
ENSE00003760341	130395211	130395347
ENSE00003920064	130398551	130398707
ENSE00003922058	130265760	130266137

Expression profiles

Bgee: expression breadth ubiquitous, 162 present calls, max score 94.85.

FANTOM5 (CAGE): breadth broad, TPM avg 0.8111 / max 66.6127, expressed in 194 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
99008	0.4450	153
99009	0.3661	128

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
pancreatic ductal cell	CL:0002079	94.85	silver quality
muscle layer of sigmoid colon	UBERON:0035805	93.03	gold quality
left ventricle myocardium	UBERON:0006566	90.85	gold quality
tendon of biceps brachii	UBERON:0008188	90.31	silver quality
saphenous vein	UBERON:0007318	90.11	gold quality
cardiac muscle of right atrium	UBERON:0003379	89.51	gold quality
small intestine Peyer’s patch	UBERON:0003454	88.80	gold quality
apex of heart	UBERON:0002098	87.60	gold quality
body of uterus	UBERON:0009853	87.43	gold quality
hindlimb stylopod muscle	UBERON:0004252	87.40	gold quality
small intestine	UBERON:0002108	86.65	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	86.25	gold quality
transverse colon	UBERON:0001157	86.17	gold quality
lower esophagus	UBERON:0013473	85.39	gold quality
lower esophagus muscularis layer	UBERON:0035833	85.34	gold quality
mucosa of transverse colon	UBERON:0004991	85.30	gold quality
colon	UBERON:0001155	84.94	gold quality
kidney epithelium	UBERON:0004819	84.87	gold quality
large intestine	UBERON:0000059	84.38	gold quality
intestine	UBERON:0000160	84.23	gold quality
ectocervix	UBERON:0012249	83.66	gold quality
endocervix	UBERON:0000458	83.48	gold quality
gastrocnemius	UBERON:0001388	83.21	gold quality
muscle of leg	UBERON:0001383	83.06	gold quality
lower esophagus mucosa	UBERON:0035834	82.54	gold quality
nasal cavity epithelium	UBERON:0005384	81.80	gold quality
upper arm skin	UBERON:0004263	81.49	gold quality
vena cava	UBERON:0004087	80.75	silver quality
mucosa of stomach	UBERON:0001199	80.41	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	80.35	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	13.76

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

13 targeting HMCN2, 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-3064-3P	100.00	70.09	1254
HSA-MIR-204-5P	99.79	71.62	2439
HSA-MIR-211-5P	99.79	71.65	2440
HSA-MIR-3196	98.96	63.91	326
HSA-MIR-3922-5P	98.77	66.53	1059
HSA-MIR-3180	98.46	64.68	348
HSA-MIR-3180-3P	98.46	64.68	348
HSA-MIR-6816-5P	98.46	64.35	364
HSA-MIR-188-5P	97.89	67.01	756
HSA-MIR-6866-3P	97.38	66.94	748
HSA-MIR-2276-5P	96.27	65.85	937
HSA-MIR-6823-5P	96.26	65.69	919
HSA-MIR-4787-5P	89.08	66.18	88

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Hmcn2	ENSMUSG00000055632
rattus_norvegicus	Hmcn2	ENSRNOG00000064166

Paralogs (36): CNTN1 (ENSG00000018236), CDON (ENSG00000064309), NEO1 (ENSG00000067141), SDK2 (ENSG00000069188), IGSF9B (ENSG00000080854), IGSF9 (ENSG00000085552), NRCAM (ENSG00000091129), MXRA5 (ENSG00000101825), IGDCC4 (ENSG00000103742), CNTN3 (ENSG00000113805), IGSF21 (ENSG00000117154), CNTN6 (ENSG00000134115), CHL1 (ENSG00000134121), PTPRQ (ENSG00000139304), CNTN4 (ENSG00000144619), BOC (ENSG00000144857), SDK1 (ENSG00000146555), NCAM1 (ENSG00000149294), CNTN5 (ENSG00000149972), IGSF10 (ENSG00000152580), ROBO4 (ENSG00000154133), ROBO3 (ENSG00000154134), NCAM2 (ENSG00000154654), VCAM1 (ENSG00000162692), NFASC (ENSG00000163531), PRTG (ENSG00000166450), ROBO1 (ENSG00000169855), DSCAM (ENSG00000171587), IGDCC3 (ENSG00000174498), VSIG10 (ENSG00000176834), DSCAML1 (ENSG00000177103), CNTN2 (ENSG00000184144), ROBO2 (ENSG00000185008), VSIG10L (ENSG00000186806), DCC (ENSG00000187323), L1CAM (ENSG00000198910)

Protein

Protein identifiers

Hemicentin-2 — Q8NDA2 (reviewed: Q8NDA2)

All UniProt accessions (4): Q8NDA2, A0A087WY63, A0A096LPG1, H0Y3X1

UniProt curated annotations — full annotation on UniProt →

Subcellular location. Secreted. Extracellular space. Extracellular matrix. Cleavage furrow.

Miscellaneous. Gene prediction based on partial EST and mRNA data. Gene prediction based on partial EST and mRNA data. Dubious isoform produced through intron retention.

Isoforms (3)

UniProt ID	Names	Canonical?
Q8NDA2-5	2	yes
Q8NDA2-1	1
Q8NDA2-4	3

RefSeq proteins (1): NP_001278744* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000152	EGF-type_Asp/Asn_hydroxyl_site	PTM
IPR000742	EGF	Domain
IPR001881	EGF-like_Ca-bd_dom	Domain
IPR003598	Ig_sub2	Domain
IPR003599	Ig_sub	Domain
IPR006605	G2_nidogen/fibulin_G2F	Domain
IPR007110	Ig-like_dom	Domain
IPR009017	GFP	Homologous_superfamily
IPR009030	Growth_fac_rcpt_cys_sf	Homologous_superfamily
IPR013098	Ig_I-set	Domain
IPR013106	Ig_V-set	Domain
IPR013783	Ig-like_fold	Homologous_superfamily
IPR018097	EGF_Ca-bd_CS	Conserved_site
IPR026823	cEGF	Domain
IPR036179	Ig-like_dom_sf	Homologous_superfamily
IPR036465	vWFA_dom_sf	Homologous_superfamily
IPR049883	NOTCH1_EGF-like	Domain
IPR050958	Cell_Adh-Cytoskel_Orgn	Family
IPR056475	GBD_Hemicentin/VWA7	Domain
IPR056861	HMCN1-like_VWA	Domain

Pfam: PF07474, PF07645, PF07679, PF12662, PF13927, PF23560, PF25106

UniProt features (156 total): disulfide bond 56, domain 49, glycosylation site 40, splice variant 4, sequence conflict 2, modified residue 2, signal peptide 1, chain 1, region of interest 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

No AlphaFold model available for Q8NDA2 — 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): 912, 917

Disulfide bonds (56): 1095–1144, 1186–1229, 1273–1323, 1367–1416, 1460–1510, 1554–1603, 1648–1697, 1741–1790, 1833–1874, 1916–1965, 2008–2059, 2101–2150, 2193–2244, 2289–2338, 2383–2432, 2476–2525, 2572–2621, 2670–2719, 2781–2830, 2876–2925 …

Glycosylation sites (40): 329, 346, 379, 478, 525, 547, 674, 1024, 1072, 1268, 1354, 1537, 1563, 1671, 1820, 1909, 2009, 2088, 2094, 2252 …

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 60 (showing top): GOBP_NEUROGENESIS, GOBP_CELL_CELL_ADHESION, GOBP_CELL_JUNCTION_ORGANIZATION, GOMF_EXTRACELLULAR_MATRIX_STRUCTURAL_CONSTITUENT, GOCC_NEURON_PROJECTION, GOBP_CELL_PROJECTION_ORGANIZATION, GOCC_BASEMENT_MEMBRANE, PETRETTO_HEART_MASS_QTL_CIS_UP, GOCC_CELL_DIVISION_SITE, GOCC_PLASMA_MEMBRANE_REGION, GOCC_CELL_BODY, GOCC_SOMATODENDRITIC_COMPARTMENT, GOCC_AXON, GOMF_TRANSMEMBRANE_SIGNALING_RECEPTOR_ACTIVITY, GOMF_STRUCTURAL_MOLECULE_ACTIVITY

GO Biological Process (4): homophilic cell-cell adhesion (GO:0007156), synapse organization (GO:0050808), cell adhesion (GO:0007155), axon guidance (GO:0007411)

GO Molecular Function (3): calcium ion binding (GO:0005509), axon guidance receptor activity (GO:0008046), extracellular matrix structural constituent (GO:0005201)

GO Cellular Component (10): extracellular region (GO:0005576), basement membrane (GO:0005604), plasma membrane (GO:0005886), cell cortex (GO:0005938), cell junction (GO:0030054), axon (GO:0030424), extracellular matrix (GO:0031012), cleavage furrow (GO:0032154), neuronal cell body (GO:0043025), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
extracellular matrix	2
cell periphery	2
cell-cell adhesion	1
cell junction organization	1
cellular process	1
axonogenesis	1
neuron projection guidance	1
metal ion binding	1
transmembrane signaling receptor activity	1
axon guidance	1
structural molecule activity	1
membrane	1
cytoplasm	1
neuron projection	1
external encapsulating structure	1
cell division site	1
plasma membrane region	1
somatodendritic compartment	1
cell body	1

Protein interactions and networks

STRING

646 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
HMCN2	SLC36A3	Q495N2	556
HMCN2	HDGFL3	Q9Y3E1	447
HMCN2	GPX3	P22352	409
HMCN2	NTM	Q9P121	397
HMCN2	PON3	Q15166	371
HMCN2	OR14A16	Q8NHC5	369
HMCN2	OR11L1	Q8NGX0	358
HMCN2	OR6F1	Q8NGZ6	331
HMCN2	SLAMF1	Q13291	329
HMCN2	RIBC1	Q8N443	325
HMCN2	DEPDC4	Q8N2C3	325
HMCN2	FAM47A	Q5JRC9	322
HMCN2	FREM2	Q5SZK8	320
HMCN2	KRTAP4-8	Q9BYQ9	320
HMCN2	NPIPB12	F8W0I5	302

IntAct

0 interactions, top by confidence:

ESM2 similar proteins: A0A140LHF2, A0JPB1, A2AJ76, A7LCJ3, A8E0Y8, E7FF10, O00241, O60500, P01874, P03988, P04221, P0DOX2, P0DOX3, P0DOX4, P0DOX6, P0DP72, P32507, P35590, P43121, P50895, Q06805, Q06806, Q148M6, Q15109, Q5TFQ8, Q5U5A3, Q5XI43, Q62230, Q62786, Q8HW98, Q8NDA2, Q8R2Y2, Q92154, Q923P0, Q93033, Q95KI3, Q96MS0, Q9BRK3, Q9BZZ2, Q9DBV4

Diamond homologs: A0N0X6, A2AJ76, A2CG49, A4IGL7, A4IIW9, B3NS99, B4GBH0, B4HNW4, B4KPU0, B4MR28, B4P5Q9, B4QC63, G5EBF1, O75325, O95428, P0C6S8, P11627, P12960, P22063, P28685, P32004, P97924, Q02246, Q07409, Q09024, Q12860, Q290N5, Q32Q07, Q3UQ28, Q3URE9, Q3V1M1, Q5R482, Q61330, Q61809, Q62682, Q62845, Q63198, Q66HV9, Q69Z26, Q6AWJ9

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	2
Likely benign	32
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

1264 predictions. Top by Δscore:

Variant	Effect	Δscore
9:130400778:TTTA:T	acceptor_loss	1.0000
9:130400781:A:AG	acceptor_gain	1.0000
9:130400781:AGTG:A	acceptor_loss	1.0000
9:130400782:G:GA	acceptor_gain	1.0000
9:130400782:G:GC	acceptor_loss	1.0000
9:130400782:GT:G	acceptor_gain	1.0000
9:130400782:GTGC:G	acceptor_gain	1.0000
9:130402784:A:AG	acceptor_gain	1.0000
9:130402787:A:AG	acceptor_gain	1.0000
9:130402787:AGGC:A	acceptor_gain	1.0000
9:130402788:G:GA	acceptor_gain	1.0000
9:130402788:GGC:G	acceptor_gain	1.0000
9:130402788:GGCG:G	acceptor_gain	1.0000
9:130402788:GGCGC:G	acceptor_gain	1.0000
9:130402892:GCAAG:G	donor_gain	1.0000
9:130402896:GGTAA:G	donor_loss	1.0000
9:130402897:G:GG	donor_gain	1.0000
9:130402897:G:T	donor_loss	1.0000
9:130402898:T:G	donor_loss	1.0000
9:130403192:A:AG	acceptor_gain	1.0000
9:130403193:G:GG	acceptor_gain	1.0000
9:130403193:GC:G	acceptor_gain	1.0000
9:130403193:GCC:G	acceptor_gain	1.0000
9:130403307:G:GT	donor_gain	1.0000
9:130403308:A:T	donor_gain	1.0000
9:130403329:G:GG	donor_gain	1.0000
9:130403329:G:T	donor_loss	1.0000
9:130403360:G:T	donor_gain	1.0000
9:130403738:CA:C	acceptor_loss	1.0000
9:130403739:A:AG	acceptor_gain	1.0000

AlphaMissense

32621 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
9:130433539:T:G	F5009C	0.998
9:130349649:G:C	W1471C	0.997
9:130349649:G:T	W1471C	0.997
9:130375682:T:A	W2583R	0.997
9:130375682:T:C	W2583R	0.997
9:130376641:T:A	W2681R	0.997
9:130376641:T:C	W2681R	0.997
9:130349647:T:A	W1471R	0.996
9:130349647:T:C	W1471R	0.996
9:130362115:T:A	W2019R	0.996
9:130362115:T:C	W2019R	0.996
9:130375926:T:G	Y2618D	0.996
9:130379413:T:A	W2792R	0.996
9:130379413:T:C	W2792R	0.996
9:130406141:T:A	W4156R	0.996
9:130406141:T:C	W4156R	0.996
9:130406143:G:C	W4156C	0.996
9:130406143:G:T	W4156C	0.996
9:130375684:G:C	W2583C	0.995
9:130375684:G:T	W2583C	0.995
9:130379415:G:C	W2792C	0.995
9:130379415:G:T	W2792C	0.995
9:130388516:T:A	W3166R	0.995
9:130388516:T:C	W3166R	0.995
9:130362117:G:C	W2019C	0.994
9:130362117:G:T	W2019C	0.994
9:130365985:G:C	W2204C	0.994
9:130365985:G:T	W2204C	0.994
9:130375927:A:C	Y2618S	0.994
9:130376643:G:C	W2681C	0.994

dbSNP variants (sampled 300 via entrez): RS1000027245 (9:130403691 G>C), RS1000040159 (9:130363205 A>C,G), RS1000070783 (9:130431713 C>T), RS1000103153 (9:130291897 G>T), RS1000107315 (9:130327859 C>T), RS1000117752 (9:130266133 C>A,T), RS1000151602 (9:130397091 A>G), RS1000151958 (9:130339013 A>T), RS1000162700 (9:130383511 C>T), RS1000199174 (9:130407019 G>A), RS1000203606 (9:130312375 G>A), RS1000234089 (9:130383332 G>A,T), RS1000235233 (9:130357974 G>A,C,T), RS1000240779 (9:130342478 C>T), RS1000255601 (9:130265884 G>T)

Disease associations

OMIM: gene MIM:621107 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST005905_8	Global electrical heterogeneity phenotypes	2.000000e-10
GCST005905_9	Global electrical heterogeneity phenotypes	2.000000e-09
GCST009006_1	Bicuspid aortic valve without aortic dilation	2.000000e-06
GCST90011899_69	Aspartate aminotransferase levels	3.000000e-08

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004327	electrocardiography
EFO:0004736	aspartate aminotransferase 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
Benzo(a)pyrene	affects methylation, increases expression	2
methyleugenol	decreases expression	1
sodium arsenite	increases expression	1
benzo(e)pyrene	increases methylation	1
aflatoxin B2	increases methylation	1
abrine	increases expression	1
eprenetapopt	affects expression, affects reaction	1
Resveratrol	affects cotreatment, decreases expression	1
Arsenic	decreases expression	1
Benztropine	affects cotreatment, increases expression	1
Cuprizone	affects cotreatment, increases expression	1
Doxorubicin	decreases expression	1
Indomethacin	increases expression	1
Methapyrilene	increases methylation	1
Methotrexate	increases expression	1
Oxygen	increases expression	1
Phthalic Acids	increases methylation	1
Plant Extracts	affects cotreatment, decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Triclosan	increases expression	1
Aflatoxin B1	affects methylation, increases methylation	1
Okadaic Acid	increases expression	1
Permethrin	decreases expression	1

Clinical trials (associated diseases)

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