MANSC4

Summary

MANSC4 (MANSC domain containing 4, HGNC:40023) is a protein-coding gene on chromosome 12p11.22, encoding MANSC domain-containing protein 4 (A6NHS7).

Predicted to enable serine-type endopeptidase inhibitor activity. Predicted to be involved in epidermis development; epithelium development; and extracellular matrix organization. Predicted to be located in membrane. Predicted to be active in plasma membrane.

Source: NCBI Gene 100287284 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 43 total
• MANE Select transcript: NM_001146221

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:40023
Approved symbol	MANSC4
Name	MANSC domain containing 4
Location	12p11.22
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000205693
Ensembl biotype	protein_coding
Entrez	100287284

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000381273

RefSeq mRNA: 1 — MANE Select: NM_001146221 NM_001146221

CCDS: CCDS53770

Canonical transcript exons

ENST00000381273 — 4 exons

Exon	Start	End
ENSE00001488033	27762427	27763396
ENSE00001488034	27766665	27766799
ENSE00001488035	27771048	27771582
ENSE00003901961	27780210	27780236

Expression profiles

Bgee: expression breadth broad, 90 present calls, max score 78.38.

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	78.38	gold quality
cerebellar hemisphere	UBERON:0002245	57.29	gold quality
cerebellar cortex	UBERON:0002129	57.24	gold quality
cerebellum	UBERON:0002037	57.09	gold quality
placenta	UBERON:0001987	56.28	gold quality
right hemisphere of cerebellum	UBERON:0014890	55.51	gold quality
right testis	UBERON:0004534	53.35	gold quality
lymph node	UBERON:0000029	51.41	gold quality
pituitary gland	UBERON:0000007	51.38	gold quality
adenohypophysis	UBERON:0002196	50.96	gold quality
endometrium	UBERON:0001295	50.94	gold quality
testis	UBERON:0000473	50.70	gold quality
left testis	UBERON:0004533	50.17	gold quality
mucosa of stomach	UBERON:0001199	47.93	gold quality
body of pancreas	UBERON:0001150	47.12	gold quality
thoracic aorta	UBERON:0001515	46.71	gold quality
ascending aorta	UBERON:0001496	46.47	gold quality
pancreas	UBERON:0001264	46.44	gold quality
calcaneal tendon	UBERON:0003701	46.04	silver quality
descending thoracic aorta	UBERON:0002345	46.01	gold quality
right ovary	UBERON:0002118	45.99	gold quality
hypothalamus	UBERON:0001898	45.93	gold quality
body of uterus	UBERON:0009853	45.65	gold quality
right lung	UBERON:0002167	45.39	gold quality
islet of Langerhans	UBERON:0000006	45.27	gold quality
cortical plate	UBERON:0005343	45.18	gold quality
ovary	UBERON:0000992	44.60	gold quality
left ovary	UBERON:0002119	44.27	gold quality
ectocervix	UBERON:0012249	43.73	silver quality
left uterine tube	UBERON:0001303	43.68	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	2.45

Regulation

Is transcription factor: no

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Mansc4	ENSMUSG00000072662
rattus_norvegicus	Mansc4	ENSRNOG00000036925

Paralogs (2): MANSC1 (ENSG00000111261), C11orf24 (ENSG00000171067)

Protein

Protein identifiers

MANSC domain-containing protein 4 — A6NHS7 (reviewed: A6NHS7)

All UniProt accessions (1): A6NHS7

UniProt curated annotations — full annotation on UniProt →

Subcellular location. Membrane.

RefSeq proteins (1): NP_001139693* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR011106	MANSC_N	Domain
IPR013980	MANSC_dom	Domain

Pfam: PF07502

UniProt features (10 total): glycosylation site 3, topological domain 2, signal peptide 1, chain 1, transmembrane region 1, domain 1, region of interest 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-A6NHS7-F1	62.96	0.25

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Glycosylation sites (3): 118, 187, 260

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 11 (showing top): GOBP_EPITHELIUM_DEVELOPMENT, chr12p11, GOBP_EPIDERMIS_DEVELOPMENT, GOMF_PEPTIDASE_REGULATOR_ACTIVITY, GOMF_SERINE_TYPE_ENDOPEPTIDASE_INHIBITOR_ACTIVITY, GOMF_ENZYME_INHIBITOR_ACTIVITY, GOMF_ENZYME_REGULATOR_ACTIVITY, GOMF_ENDOPEPTIDASE_REGULATOR_ACTIVITY, GOBP_EXTERNAL_ENCAPSULATING_STRUCTURE_ORGANIZATION, GOMF_MOLECULAR_FUNCTION_INHIBITOR_ACTIVITY, GOMF_PEPTIDASE_INHIBITOR_ACTIVITY

GO Biological Process (3): epidermis development (GO:0008544), extracellular matrix organization (GO:0030198), epithelium development (GO:0060429)

GO Molecular Function (1): serine-type endopeptidase inhibitor activity (GO:0004867)

GO Cellular Component (2): plasma membrane (GO:0005886), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
tissue development	2
extracellular structure organization	1
external encapsulating structure organization	1
serine-type endopeptidase activity	1
endopeptidase inhibitor activity	1
membrane	1
cell periphery	1
cellular anatomical structure	1

Protein interactions and networks

STRING

388 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MANSC4	LRIT2	A6NDA9	671
MANSC4	LRIT1	Q9P2V4	618
MANSC4	TTC38	Q5R3I4	590
MANSC4	DDX28	Q9NUL7	570
MANSC4	BMS1	Q14692	532
MANSC4	CDRT15	Q96T59	418
MANSC4	CCDC91	Q7Z6B0	400
MANSC4	PRR23C	Q6ZRP0	390
MANSC4	OSGIN1	Q9UJX0	384
MANSC4	KLHL42	Q9P2K6	370
MANSC4	MAP7	Q14244	362
MANSC4	DUSP16	Q9BY84	344
MANSC4	ACMSD	Q8TDX5	344
MANSC4	ALG1L2	C9J202	332
MANSC4	CDRT4	Q8N9R6	324

IntAct

0 interactions, top by confidence:

BioGRID (2): MANSC4 (Synthetic Lethality), MANSC4 (Affinity Capture-MS)

ESM2 similar proteins: A0A1B0GVN3, A0A482APM8, A1KXM5, A4H257, A4H258, A4H259, A4H260, A6H7F9, A6NFE2, A6NHS7, A7KBS4, E9Q7F5, O74981, O75969, P09258, P09558, P19442, P22575, P80195, P88825, Q00997, Q04547, Q05100, Q2LCV6, Q2M2T8, Q30KK0, Q5NRP9, Q5QR91, Q5RAW4, Q5RBQ2, Q5RII3, Q6AXV6, Q6AXY9, Q6UW49, Q77NN4, Q7Z9I5, Q80YD3, Q810S2, Q8N4C9, Q95LJ2

Diamond homologs: A6NHS7, Q3UU94

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	37
Likely benign	4
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

507 predictions. Top by Δscore:

Variant	Effect	Δscore
12:27771044:TTACC:T	donor_loss	1.0000
12:27771045:TA:T	donor_loss	1.0000
12:27771046:A:AC	donor_gain	1.0000
12:27771046:AC:A	donor_gain	1.0000
12:27771046:ACCAT:A	donor_gain	1.0000
12:27771047:C:CA	donor_gain	1.0000
12:27771047:CC:C	donor_gain	1.0000
12:27771047:CCA:C	donor_gain	1.0000
12:27771047:CCAT:C	donor_gain	1.0000
12:27771047:CCATC:C	donor_gain	1.0000
12:27766800:C:CC	acceptor_gain	0.9900
12:27771042:ACTT:A	donor_loss	0.9900
12:27766664:CCGT:C	donor_gain	0.9800
12:27768993:G:A	donor_gain	0.9800
12:27763395:ACC:A	acceptor_loss	0.9700
12:27763397:CTGAA:C	acceptor_loss	0.9700
12:27763398:T:C	acceptor_loss	0.9700
12:27769303:T:A	donor_gain	0.9600
12:27763397:C:CC	acceptor_gain	0.9300
12:27763399:GAAAA:G	acceptor_loss	0.9200
12:27763400:AAAAA:A	acceptor_loss	0.9200
12:27763392:TATAC:T	acceptor_gain	0.9100
12:27769233:TAAG:T	donor_gain	0.9100
12:27769234:AAGA:A	donor_gain	0.9100
12:27771108:T:TA	donor_gain	0.9100
12:27763394:TAC:T	acceptor_gain	0.9000
12:27769115:A:T	acceptor_gain	0.9000
12:27766795:GGAAA:G	acceptor_gain	0.8900
12:27763401:AAAA:A	acceptor_loss	0.8800
12:27769030:CTG:C	donor_gain	0.8800

AlphaMissense

2239 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:27766744:G:C	C95W	0.993
12:27766731:A:G	C100R	0.992
12:27766745:C:G	C95S	0.992
12:27766746:A:G	C95R	0.992
12:27766746:A:T	C95S	0.992
12:27766793:C:T	C79Y	0.992
12:27771077:C:G	C67S	0.992
12:27771078:A:T	C67S	0.992
12:27766777:G:C	F84L	0.991
12:27766777:G:T	F84L	0.991
12:27766779:A:G	F84L	0.991
12:27766793:C:G	C79S	0.991
12:27766794:A:T	C79S	0.991
12:27771064:G:C	C71W	0.991
12:27771078:A:G	C67R	0.991
12:27766713:A:G	C106R	0.990
12:27766729:G:C	C100W	0.990
12:27766730:C:G	C100S	0.990
12:27766731:A:T	C100S	0.990
12:27766784:G:T	A82D	0.990
12:27766792:A:C	C79W	0.990
12:27766794:A:G	C79R	0.990
12:27771061:A:C	C72W	0.989
12:27771065:C:T	C71Y	0.989
12:27771076:G:C	C67W	0.989
12:27771178:G:C	C33W	0.989
12:27766711:G:C	C106W	0.988
12:27766793:C:A	C79F	0.988
12:27771066:A:G	C71R	0.988
12:27771175:C:A	W34C	0.988

dbSNP variants (sampled 300 via entrez): RS1000153874 (12:27767476 G>C), RS1000206585 (12:27767685 G>A,C), RS1000471735 (12:27776383 T>G), RS1000740075 (12:27763672 G>A), RS1000890553 (12:27779052 A>G), RS1000940955 (12:27779255 G>A), RS1001056456 (12:27772359 C>T), RS1001198951 (12:27764226 A>G), RS1001231452 (12:27764405 GC>G), RS1001504730 (12:27773375 T>G), RS1001654799 (12:27766742 A>T), RS1001776438 (12:27781809 A>G), RS1001881638 (12:27775720 C>T), RS1001894270 (12:27771854 T>C), RS1001933763 (12:27775946 C>T)

Disease associations

OMIM: gene `` | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST006585_1135	Blood protein levels	7.000000e-200
GCST010796_4831	Electrocardiogram morphology (amplitude at temporal datapoints)	3.000000e-08

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004327	electrocardiography

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

2 total (human), top 2 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
aristolochic acid I	increases expression	1
Benzo(a)pyrene	increases methylation	1

Clinical trials (associated diseases)

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