CWH43

Summary

CWH43 (cell wall biogenesis 43 C-terminal homolog, HGNC:26133) is a protein-coding gene on chromosome 4p11, encoding PGAP2-interacting protein (Q9H720). Involved in lipid remodeling during GPI-anchor maturation.

Predicted to be involved in GPI anchor biosynthetic process. Predicted to act upstream of or within several processes, including cerebrospinal fluid circulation; establishment of protein localization; and protein N-linked glycosylation. Predicted to be located in extracellular region and membrane. Predicted to be active in endoplasmic reticulum.

Source: NCBI Gene 80157 — RefSeq curated summary.

At a glance

• GWAS associations: 5
• Clinical variants (ClinVar): 107 total
• MANE Select transcript: NM_025087

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:26133
Approved symbol	CWH43
Name	cell wall biogenesis 43 C-terminal homolog
Location	4p11
Locus type	gene with protein product
Status	Approved
Aliases	FLJ21511, CWH43-C, PGAP2IP
Ensembl gene	ENSG00000109182
Ensembl biotype	protein_coding
OMIM	618561
Entrez	80157

Gene structure

Transcript identifiers

Ensembl transcripts: 16 — 13 protein_coding, 2 retained_intron, 1 nonsense_mediated_decay

ENST00000226432, ENST00000506221, ENST00000507372, ENST00000513409, ENST00000514053, ENST00000856985, ENST00000856986, ENST00000856987, ENST00000856988, ENST00000856989, ENST00000856990, ENST00000856991, ENST00000856992, ENST00000856993, ENST00000948154, ENST00000948155

RefSeq mRNA: 2 — MANE Select: NM_025087 NM_001286791, NM_025087

CCDS: CCDS3486, CCDS68697

Canonical transcript exons

ENST00000226432 — 16 exons

Exon	Start	End
ENSE00000714566	48991936	48992090
ENSE00000714606	48994619	48994820
ENSE00000847078	48991454	48991574
ENSE00000847079	48998460	48998548
ENSE00000847080	49003735	49003992
ENSE00001209849	49061812	49062079
ENSE00001209889	48986275	48986472
ENSE00003469086	48988477	48988668
ENSE00003504551	49032566	49032715
ENSE00003517355	49050694	49050849
ENSE00003534085	49007201	49007326
ENSE00003566243	49028629	49028734
ENSE00003579241	49030825	49030960
ENSE00003590010	49038036	49038180
ENSE00003621105	49017249	49017328
ENSE00003679615	49044786	49044847

Expression profiles

Bgee: expression breadth ubiquitous, 155 present calls, max score 97.37.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.3579 / max 102.8406, expressed in 79 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
47601	0.2211	63
47602	0.0768	35
47600	0.0600	33

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
tongue squamous epithelium	UBERON:0006919	97.37	gold quality
cervix squamous epithelium	UBERON:0006922	95.96	gold quality
gingival epithelium	UBERON:0001949	94.96	gold quality
squamous epithelium	UBERON:0006914	94.78	gold quality
gingiva	UBERON:0001828	94.63	gold quality
esophagus squamous epithelium	UBERON:0006920	94.30	gold quality
epithelium of esophagus	UBERON:0001976	93.47	gold quality
hair follicle	UBERON:0002073	93.41	gold quality
cervix epithelium	UBERON:0004801	93.40	gold quality
upper arm skin	UBERON:0004263	93.19	gold quality
skin of leg	UBERON:0001511	91.61	gold quality
colonic mucosa	UBERON:0000317	91.56	gold quality
skin of abdomen	UBERON:0001416	91.55	gold quality
zone of skin	UBERON:0000014	91.29	gold quality
mucosa of sigmoid colon	UBERON:0004993	91.11	gold quality
mammalian vulva	UBERON:0000997	90.97	gold quality
upper leg skin	UBERON:0004262	90.51	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	90.09	gold quality
lower esophagus mucosa	UBERON:0035834	89.60	gold quality
mucosa of transverse colon	UBERON:0004991	89.08	gold quality
oviduct epithelium	UBERON:0004804	88.32	gold quality
esophagus mucosa	UBERON:0002469	87.00	gold quality
skin of hip	UBERON:0001554	86.56	gold quality
rectum	UBERON:0001052	86.16	gold quality
penis	UBERON:0000989	86.14	gold quality
prostate gland	UBERON:0002367	82.81	gold quality
nephron tubule	UBERON:0001231	81.97	gold quality
oral cavity	UBERON:0000167	81.74	gold quality
bronchial epithelial cell	CL:0002328	81.57	gold quality
right uterine tube	UBERON:0001302	81.25	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	7.97

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

17 targeting CWH43, 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-188-3P	100.00	68.76	1240
HSA-MIR-539-5P	99.93	70.30	2855
HSA-MIR-10527-5P	99.91	72.28	3754
HSA-MIR-4503	99.85	71.45	1869
HSA-MIR-4307	99.82	70.45	3374
HSA-MIR-3156-3P	99.76	66.72	939
HSA-MIR-200A-5P	99.76	69.10	949
HSA-MIR-200B-5P	99.76	69.05	948
HSA-MIR-4446-5P	99.72	69.19	2544
HSA-MIR-33A-3P	99.70	70.27	3362
HSA-MIR-1260A	99.61	66.67	1098
HSA-MIR-1260B	99.61	66.67	1098
HSA-MIR-1-5P	98.70	68.66	1017
HSA-MIR-7977	98.65	66.18	2590
HSA-MIR-10226	98.25	66.50	811
HSA-MIR-22-5P	97.67	68.92	1355
HSA-MIR-4301	95.00	65.22	554

Literature-anchored findings (GeneRIF, showing 2)

• Increased plasmin-mediated proteolysis of L1CAM in a mouse model of idiopathic normal pressure hydrocephalus. (PMID:34380733)
• CWH43 Is a Novel Tumor Suppressor Gene with Negative Regulation of TTK in Colorectal Cancer. (PMID:37894942)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Cwh43	ENSMUSG00000029154
rattus_norvegicus	Cwh43	ENSRNOG00000002174

Protein

Protein identifiers

PGAP2-interacting protein — Q9H720 (reviewed: Q9H720)

Alternative names: Cell wall biogenesis protein 43 C-terminal homolog

All UniProt accessions (3): Q9H720, D6RDZ8, E7EQL2

UniProt curated annotations — full annotation on UniProt →

Function. Involved in lipid remodeling during GPI-anchor maturation.

Subunit / interactions. Interacts with PGAP2/FRAG1.

Subcellular location. Membrane.

Similarity. Belongs to the PGAP2IP family.

RefSeq proteins (2): NP_001273720, NP_079363* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR036691	Endo/exonu/phosph_ase_sf	Homologous_superfamily
IPR051916	GPI-anchor_lipid_remodeler	Family
IPR053911	PGAP2IP_TM_2nd	Domain
IPR053912	PGAP2IP_TM_1nd	Domain
IPR057315	Exo_endo_phos_PGAP2IP_C	Domain

Pfam: PF23021, PF23022, PF23226

UniProt features (15 total): transmembrane region 10, sequence variant 2, chain 1, region of interest 1, glycosylation site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9H720-F1	91.45	0.81

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 (1): 455

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 147 (showing top): GOBP_PHOSPHOLIPID_METABOLIC_PROCESS, BENPORATH_ES_WITH_H3K27ME3, GOBP_PHOSPHATIDYLINOSITOL_METABOLIC_PROCESS, GOBP_BEHAVIOR, GOBP_INTRACELLULAR_PROTEIN_TRANSPORT, GOBP_GLYCOLIPID_BIOSYNTHETIC_PROCESS, JAEGER_METASTASIS_DN, GOBP_PROTEIN_N_LINKED_GLYCOSYLATION, GOBP_PROTEIN_TARGETING, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, GOBP_ESTABLISHMENT_OF_PROTEIN_LOCALIZATION_TO_ORGANELLE, CHANDRAN_METASTASIS_DN, GOBP_ORGANOPHOSPHATE_BIOSYNTHETIC_PROCESS, ONDER_CDH1_TARGETS_3_DN, GOBP_NEUROMUSCULAR_PROCESS_CONTROLLING_BALANCE

GO Biological Process (23): peptide secretion (GO:0002790), protein N-linked glycosylation (GO:0006487), GPI anchor biosynthetic process (GO:0006506), membrane protein ectodomain proteolysis (GO:0006509), protein import into nucleus (GO:0006606), protein targeting to membrane (GO:0006612), cell adhesion (GO:0007155), brain development (GO:0007420), regulation of protein import into nucleus (GO:0042306), cilium organization (GO:0044782), neuromuscular process controlling balance (GO:0050885), regulation of protein processing (GO:0070613), protein localization to extracellular region (GO:0071692), walking behavior (GO:0090659), cerebrospinal fluid circulation (GO:0090660), regulation of intracellular signal transduction (GO:1902531), obsolete protein glycosylation (GO:0006486), proteolysis (GO:0006508), intracellular protein localization (GO:0008104), gene expression (GO:0010467), regulation of protein localization (GO:0032880), membrane protein proteolysis (GO:0033619), regulation of protein localization to nucleus (GO:1900180)

GO Molecular Function (0):

GO Cellular Component (3): extracellular region (GO:0005576), endoplasmic reticulum (GO:0005783), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
macromolecule localization	2
cellular anatomical structure	2
peptide transport	1
secretion	1
glycoprotein biosynthetic process	1
GPI anchor metabolic process	1
glycolipid biosynthetic process	1
glycerophospholipid biosynthetic process	1
GPI anchored protein biosynthesis	1
membrane protein proteolysis	1
intracellular protein transport	1
protein localization to nucleus	1
import into nucleus	1
establishment of protein localization to organelle	1
protein targeting	1
establishment of protein localization to membrane	1
cellular process	1
central nervous system development	1
animal organ development	1
head development	1
protein import into nucleus	1
regulation of intracellular protein transport	1
regulation of nucleocytoplasmic transport	1
regulation of protein localization to nucleus	1
organelle organization	1
plasma membrane bounded cell projection organization	1
musculoskeletal movement	1
neuromuscular process	1
protein processing	1
regulation of proteolysis	1
regulation of protein maturation	1
locomotory behavior	1
epithelial cilium movement involved in extracellular fluid movement	1
nervous system process	1
regulation of signal transduction	1
intracellular signal transduction	1
protein metabolic process	1
macromolecule biosynthetic process	1
cytoplasm	1
endomembrane system	1

Protein interactions and networks

STRING

708 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CWH43	PGAP2	Q9UHJ9	588
CWH43	DCUN1D4	Q92564	581
CWH43	PGAP3	Q96FM1	508
CWH43	CRACDL	Q6NV74	505
CWH43	CAPN9	O14815	501
CWH43	PGAP1	Q75T13	494
CWH43	TOM1L1	O75674	462
CWH43	WDR93	Q6P2C0	450
CWH43	OR51T1	Q8NGJ9	428
CWH43	CFAP43	Q8NDM7	423
CWH43	BAIAP2L1	Q9UHR4	417
CWH43	HEPACAM	Q14CZ8	416
CWH43	DEFB115	Q30KQ5	416
CWH43	KIF18A	Q8NI77	406
CWH43	EPB41	P11171	399
CWH43	R3HDM2	Q9Y2K5	399

IntAct

3 interactions, top by confidence:

A	B	Type	Score
CWH43	H1-2	psi-mi:“MI:0915”(physical association)	0.400
CCR1	UBA6	psi-mi:“MI:0914”(association)	0.350

BioGRID (2): CWH43 (Proximity Label-MS), CWH43 (Affinity Capture-MS)

ESM2 similar proteins: A5D8M0, A7YWI9, A8XU68, B8A4F4, D3ZGS3, F1QG30, G5ECL2, O15056, O18964, O43001, O43426, O45870, O55207, O74369, O95551, P17625, P34370, P38207, P40015, P87175, Q01968, Q03210, Q03264, Q08227, Q08DF7, Q17848, Q21407, Q24239, Q28FQ5, Q3T1H5, Q3TIU4, Q5XJA0, Q62910, Q6AXQ5, Q6L8Q7, Q6NVF0, Q755C1, Q75AW4, Q75B12, Q7YTB0

Diamond homologs: P25618, Q9H720, Q9HDZ2, Q91YL7

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	93
Likely benign	7
Benign	3

Top pathogenic / likely-pathogenic (0)

SpliceAI

2787 predictions. Top by Δscore:

Variant	Effect	Δscore
4:49007196:AACAG:A	acceptor_gain	1.0000
4:49007322:ACTTT:A	donor_gain	1.0000
4:49007323:CTTT:C	donor_gain	1.0000
4:49007325:TT:T	donor_gain	1.0000
4:49007327:G:GG	donor_gain	1.0000
4:49032716:G:GG	donor_gain	1.0000
4:49050848:AGGTG:A	donor_loss	1.0000
4:49050850:GTG:G	donor_loss	1.0000
4:49050851:T:A	donor_loss	1.0000
4:49061807:TTTA:T	acceptor_loss	1.0000
4:49061808:TTAG:T	acceptor_loss	1.0000
4:49061809:TAG:T	acceptor_loss	1.0000
4:49061810:AGA:A	acceptor_loss	1.0000
4:48988476:GGAT:G	acceptor_gain	0.9900
4:48991559:G:GT	donor_gain	0.9900
4:48992179:T:TA	donor_gain	0.9900
4:48992180:A:AA	donor_gain	0.9900
4:49007324:TTT:T	donor_gain	0.9900
4:49032674:C:T	donor_gain	0.9900
4:49032714:GA:G	donor_gain	0.9900
4:49038034:A:AG	acceptor_gain	0.9900
4:49038035:G:C	acceptor_gain	0.9900
4:49038035:G:GG	acceptor_gain	0.9900
4:49038035:GA:G	acceptor_gain	0.9900
4:49038035:GAGAT:G	acceptor_gain	0.9900
4:49038178:AAG:A	donor_gain	0.9900
4:49044780:TATTA:T	acceptor_loss	0.9900
4:49044783:TA:T	acceptor_loss	0.9900
4:49044784:A:AC	acceptor_loss	0.9900
4:49044785:G:A	acceptor_loss	0.9900

AlphaMissense

4569 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
4:49030851:A:C	S467R	0.993
4:49030853:T:A	S467R	0.993
4:49030853:T:G	S467R	0.993
4:49038061:G:C	A562P	0.990
4:49030956:T:A	W502R	0.988
4:49030956:T:C	W502R	0.988
4:49030849:A:T	E466V	0.986
4:49030959:G:T	G503W	0.986
4:49030933:G:A	G494D	0.985
4:49044812:A:C	R610S	0.985
4:49044812:A:T	R610S	0.985
4:49050728:A:C	S634R	0.985
4:49050730:T:A	S634R	0.985
4:49050730:T:G	S634R	0.985
4:49003944:T:C	F338L	0.984
4:49003946:T:A	F338L	0.984
4:49003946:T:G	F338L	0.984
4:49028671:T:C	F437L	0.984
4:49028673:T:A	F437L	0.984
4:49028673:T:G	F437L	0.984
4:49050756:T:C	F643S	0.984
4:49028659:T:A	W433R	0.983
4:49028659:T:C	W433R	0.983
4:48994771:T:A	W222R	0.982
4:48994771:T:C	W222R	0.982
4:49044811:G:C	R610T	0.982
4:49032645:G:C	A530P	0.981
4:49030959:G:A	G503R	0.979
4:49030959:G:C	G503R	0.979
4:49038115:G:A	G580R	0.979

dbSNP variants (sampled 300 via entrez): RS1000098593 (4:49027935 G>T), RS1000207297 (4:49061168 C>G,T), RS1000214681 (4:48992931 A>G), RS1000273267 (4:48986202 C>A,G,T), RS1000295461 (4:49027440 G>A), RS1000362966 (4:49054432 T>G), RS1000368433 (4:49038975 A>G), RS1000573192 (4:49026206 C>T), RS1000622724 (4:48991119 T>A), RS1000627169 (4:48988177 CCTACAGATATA>C), RS1000701227 (4:49037857 C>A), RS1000730854 (4:49032059 G>A,C), RS1000802162 (4:48992566 A>C), RS1000836841 (4:49037692 AT>A), RS1000894709 (4:48997878 A>G)

Disease associations

OMIM: gene MIM:618561 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

5 associations (top):

Study	Trait	p-value
GCST001325_3	Response to hepatitis C treatment	8.000000e-06
GCST006462_17	Uterine fibroids	3.000000e-13
GCST007094_157	Diastolic blood pressure	6.000000e-06
GCST007099_37	Systolic blood pressure	2.000000e-08
GCST008059_239	Estimated glomerular filtration rate	5.000000e-10

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0006336	diastolic blood pressure
EFO:0006335	systolic blood pressure

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

14 total (human), top 14 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol S	affects cotreatment, increases methylation, decreases expression	2
Benzo(a)pyrene	decreases expression, increases methylation	2
sodium arsenate	decreases expression, increases abundance	1
2-methyl-2H-pyrazole-3-carboxylic acid (2-methyl-4-o-tolylazophenyl)amide	decreases expression, decreases reaction	1
Fulvestrant	increases methylation, affects cotreatment	1
Arsenic	decreases expression, increases abundance	1
Vehicle Emissions	decreases reaction, decreases expression	1
Progesterone	decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Valproic Acid	increases expression	1
Vitamin E	decreases expression	1
Cadmium Chloride	increases expression	1
Lactic Acid	decreases expression	1
Particulate Matter	decreases expression, decreases reaction	1

Clinical trials (associated diseases)

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