NOMO2

Summary

NOMO2 (NODAL modulator 2, HGNC:22652) is a protein-coding gene on chromosome 16p12.3, encoding BOS complex subunit NOMO2 (Q5JPE7). Component of the multi-pass translocon (MPT) complex that mediates insertion of multi-pass membrane proteins into the lipid bilayer of membranes.

This gene encodes a protein originally thought to be related to the collagenase gene family. This gene is one of three highly similar genes in a region of duplication located on the p arm of chromosome 16. These three genes encode closely related proteins that may have the same function. The protein encoded by one of these genes has been identified as part of a protein complex that participates in the Nodal signaling pathway during vertebrate development. Mutations in ABCC6, which is located nearby, rather than mutations in this gene are associated with pseudoxanthoma elasticum (PXE). Two transcripts encoding different isoforms have been described.

Source: NCBI Gene 283820 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 123 total
• MANE Select transcript: NM_173614

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:22652
Approved symbol	NOMO2
Name	NODAL modulator 2
Location	16p12.3
Locus type	gene with protein product
Status	Approved
Aliases	NOMO, PM5
Ensembl gene	ENSG00000185164
Ensembl biotype	protein_coding
OMIM	609158
Entrez	283820

Gene structure

Transcript identifiers

Ensembl transcripts: 16 — 10 protein_coding, 4 nonsense_mediated_decay, 2 retained_intron

ENST00000330537, ENST00000381474, ENST00000543392, ENST00000562312, ENST00000564355, ENST00000564991, ENST00000567831, ENST00000569051, ENST00000569526, ENST00000621364, ENST00000622306, ENST00000897970, ENST00000933160, ENST00000933161, ENST00000961670, ENST00000961671

RefSeq mRNA: 2 — MANE Select: NM_173614 NM_001004060, NM_173614

CCDS: CCDS10570, CCDS32394

Canonical transcript exons

ENST00000622306 — 31 exons

Exon	Start	End
ENSE00001717766	18549521	18549627
ENSE00003462100	18531466	18531607
ENSE00003463777	18542172	18542261
ENSE00003470425	18551439	18551539
ENSE00003482282	18523844	18523939
ENSE00003495691	18557702	18557791
ENSE00003496347	18520765	18520983
ENSE00003514234	18547228	18547300
ENSE00003522091	18527537	18527624
ENSE00003528474	18519501	18519660
ENSE00003537721	18531037	18531168
ENSE00003546802	18520597	18520679
ENSE00003560140	18554807	18554852
ENSE00003571460	18542594	18542731
ENSE00003579218	18538526	18538676
ENSE00003650234	18538859	18538964
ENSE00003655349	18524489	18524552
ENSE00003656194	18519229	18519355
ENSE00003677901	18529501	18529637
ENSE00003679987	18533005	18533179
ENSE00003689354	18543617	18543769
ENSE00003716518	18513350	18513433
ENSE00003720873	18506873	18506992
ENSE00003721243	18499927	18500567
ENSE00003721386	18511546	18511656
ENSE00003724208	18517189	18517302
ENSE00003725388	18514342	18514483
ENSE00003736514	18509166	18509267
ENSE00003736786	18515883	18516010
ENSE00003752543	18500991	18501083
ENSE00003916146	18561876	18562097

Expression profiles

Bgee: expression breadth ubiquitous, 134 present calls, max score 98.77.

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
body of pancreas	UBERON:0001150	98.77	gold quality
superior frontal gyrus	UBERON:0002661	98.67	gold quality
primary visual cortex	UBERON:0002436	98.58	gold quality
Brodmann (1909) area 9	UBERON:0013540	98.54	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	98.32	gold quality
right frontal lobe	UBERON:0002810	98.22	gold quality
nucleus accumbens	UBERON:0001882	98.18	gold quality
pancreas	UBERON:0001264	98.11	gold quality
right atrium auricular region	UBERON:0006631	98.02	gold quality
anterior cingulate cortex	UBERON:0009835	97.84	gold quality
apex of heart	UBERON:0002098	97.76	gold quality
hypothalamus	UBERON:0001898	97.74	gold quality
stromal cell of endometrium	CL:0002255	97.61	gold quality
pituitary gland	UBERON:0000007	97.58	gold quality
right hemisphere of cerebellum	UBERON:0014890	97.54	gold quality
adenohypophysis	UBERON:0002196	97.47	gold quality
cerebellum	UBERON:0002037	97.43	gold quality
heart left ventricle	UBERON:0002084	97.43	gold quality
cerebellar cortex	UBERON:0002129	97.41	gold quality
cerebellar hemisphere	UBERON:0002245	97.38	gold quality
islet of Langerhans	UBERON:0000006	97.36	gold quality
putamen	UBERON:0001874	97.33	gold quality
caudate nucleus	UBERON:0001873	97.31	gold quality
heart	UBERON:0000948	97.25	gold quality
Ammon’s horn	UBERON:0001954	97.23	gold quality
brain	UBERON:0000955	97.14	gold quality
cerebral cortex	UBERON:0000956	96.99	gold quality
ascending aorta	UBERON:0001496	96.98	gold quality
thoracic aorta	UBERON:0001515	96.95	gold quality
substantia nigra	UBERON:0002038	96.86	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	12.72

Regulation

Is transcription factor: no

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	nomo	ENSDARG00000078592
mus_musculus	Nomo1	ENSMUSG00000030835
rattus_norvegicus	Nomo1	ENSRNOG00000021118
drosophila_melanogaster	CG1371	FBGN0033482
caenorhabditis_elegans		WBGENE00015344

Paralogs (2): NOMO3 (ENSG00000103226), NOMO1 (ENSG00000103512)

Protein

Protein identifiers

BOS complex subunit NOMO2 — Q5JPE7 (reviewed: Q5JPE7)

Alternative names: Nodal modulator 2, pM5 protein 2

All UniProt accessions (5): Q5JPE7, H3BMJ6, H3BNC4, H3BPS9, H3BTW1

UniProt curated annotations — full annotation on UniProt →

Function. Component of the multi-pass translocon (MPT) complex that mediates insertion of multi-pass membrane proteins into the lipid bilayer of membranes. The MPT complex takes over after the SEC61 complex: following membrane insertion of the first few transmembrane segments of proteins by the SEC61 complex, the MPT complex occludes the lateral gate of the SEC61 complex to promote insertion of subsequent transmembrane regions.

Subunit / interactions. Component of the back of Sec61 (BOS) complex, composed of NCLN/Nicalin, NOMO (NOMO1, NOMO2 or NOMO3) and TMEM147. The BOS complex is part of the multi-pass translocon (MPT) complex, composed of three subcomplexes, the GEL complex (composed of RAB5IF/OPTI and TMCO1), the BOS complex (composed of NCLN/Nicalin, NOMO and TMEM147) and the PAT complex (composed of WDR83OS/Asterix and CCDC47). The MPT complex associates with the SEC61 complex. Due to the strong similarity between NOMO1, NOMO2 and NOMO3, similar interaction pattern probably occur for the three gene copies.

Subcellular location. Endoplasmic reticulum membrane.

Tissue specificity. Highly expressed in pancreas and skeletal muscle and, at lower levels, in heart.

Isoforms (3)

UniProt ID	Names	Canonical?
Q5JPE7-1	1	yes
Q5JPE7-2	2
Q5JPE7-3	3

RefSeq proteins (2): NP_001004060, NP_775885* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR008969	CarboxyPept-like_regulatory	Homologous_superfamily
IPR013783	Ig-like_fold	Homologous_superfamily
IPR013784	Carb-bd-like_fold	Homologous_superfamily
IPR041033	SpaA_PFL_dom_1	Domain
IPR051417	SDr/BOS_complex	Family
IPR055073	NOMO1-like_9th	Domain
IPR055074
IPR055075	NOMO-like_N	Domain
IPR056187	NOMO_8th	Domain
IPR056189	NOMO_3rd	Domain
IPR056190	NOMO_5th	Domain
IPR056191	NOMO_12th	Domain
IPR056319	NOMO_7th	Domain

Pfam: PF13620, PF17802, PF22898, PF22902, PF22904, PF23141, PF23192, PF23193, PF23194, PF23660

UniProt features (14 total): splice variant 3, glycosylation site 3, sequence variant 2, topological domain 2, signal peptide 1, chain 1, transmembrane region 1, region of interest 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
9C7U	ELECTRON MICROSCOPY	3.65
9C7V	ELECTRON MICROSCOPY	6.6

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q5JPE7-F1	79.72	0.31

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): 50, 218, 618

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 40 (showing top): GOBP_ESTABLISHMENT_OF_PROTEIN_LOCALIZATION_TO_MEMBRANE, GOBP_ENDOMEMBRANE_SYSTEM_ORGANIZATION, GOBP_PROTEIN_LOCALIZATION_TO_ORGANELLE, GOBP_MEMBRANE_ORGANIZATION, GOBP_ENDOPLASMIC_RETICULUM_ORGANIZATION, GOBP_LOCALIZATION_WITHIN_MEMBRANE, GOBP_PROTEIN_INSERTION_INTO_MEMBRANE, ACEVEDO_LIVER_CANCER_WITH_H3K27ME3_DN, chr16p12, GOCC_NUCLEAR_OUTER_MEMBRANE_ENDOPLASMIC_RETICULUM_MEMBRANE_NETWORK, GOCC_ORGANELLE_SUBCOMPARTMENT, GOMF_RIBONUCLEOPROTEIN_COMPLEX_BINDING, GOMF_RIBOSOME_BINDING, GOBP_PROTEIN_INSERTION_INTO_ER_MEMBRANE, GOCC_ER_MEMBRANE_INSERTION_COMPLEX

GO Biological Process (1): multi-pass transmembrane protein insertion into ER membrane (GO:0160063)

GO Molecular Function (3): carbohydrate binding (GO:0030246), ribosome binding (GO:0043022), protein binding (GO:0005515)

GO Cellular Component (5): endoplasmic reticulum membrane (GO:0005789), protein-containing complex (GO:0032991), multi-pass translocon complex (GO:0160064), endoplasmic reticulum (GO:0005783), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
binding	2
protein insertion into ER membrane	1
ribonucleoprotein complex binding	1
organelle membrane	1
nuclear outer membrane-endoplasmic reticulum membrane network	1
endoplasmic reticulum subcompartment	1
cellular_component	1
ER membrane insertion complex	1
cytoplasm	1
endomembrane system	1
intracellular membrane-bounded organelle	1
cellular anatomical structure	1

Protein interactions and networks

STRING

330 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NOMO2	NCLN	Q969V3	993
NOMO2	TMEM147	Q9BVK8	986
NOMO2	XYLT1	Q86Y38	801
NOMO2	DENR	O43583	717
NOMO2	FCF1	Q9Y324	715
NOMO2	ABCC6	P78420	701
NOMO2	NCSTN	Q92542	576
NOMO2	TNXB	P22105	572
NOMO2	PACC1	Q9H813	570
NOMO2	SLC9C1	Q4G0N8	507
NOMO2	PNCK	Q6P2M8	507
NOMO2	TNN	Q9UQP3	476
NOMO2	KCNV1	Q6PIU1	447
NOMO2	ATF7IP	Q6VMQ6	434
NOMO2	TAPBP	O15533	431

IntAct

35 interactions, top by confidence:

A	B	Type	Score
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
NOMO2	NCLN	psi-mi:“MI:0915”(physical association)	0.670
	GNAT3	psi-mi:“MI:0915”(physical association)	0.400
NOMO2	PA	psi-mi:“MI:0915”(physical association)	0.370
NOMO2	PB2	psi-mi:“MI:0915”(physical association)	0.370
STAT1	NOMO2	psi-mi:“MI:0915”(physical association)	0.370
NOMO2	UBE3A	psi-mi:“MI:0915”(physical association)	0.370
TAGLN	LOC392647	psi-mi:“MI:0914”(association)	0.350
SLC16A11	ESYT2	psi-mi:“MI:0914”(association)	0.350
MYC		psi-mi:“MI:0914”(association)	0.350
CAPRIN1	EIF3CL	psi-mi:“MI:0914”(association)	0.350
DRG1	RPS3A	psi-mi:“MI:0914”(association)	0.350
G3BP2	RPS3A	psi-mi:“MI:0914”(association)	0.350
HMGB2	EIF3CL	psi-mi:“MI:0914”(association)	0.350
METAP2	EIF3CL	psi-mi:“MI:0914”(association)	0.350
NOMO1	RNF40	psi-mi:“MI:0914”(association)	0.350
PSPC1	MCRIP1	psi-mi:“MI:0914”(association)	0.350
RACK1	RPS3A	psi-mi:“MI:0914”(association)	0.350
RBM8A	MCRIP1	psi-mi:“MI:0914”(association)	0.350
RPS16	MCRIP1	psi-mi:“MI:0914”(association)	0.350
SRP19	RPS3A	psi-mi:“MI:0914”(association)	0.350
SRP9	RPS3A	psi-mi:“MI:0914”(association)	0.350
TMEM147	RPL22	psi-mi:“MI:0914”(association)	0.350
TPT1	RPL13	psi-mi:“MI:0914”(association)	0.350
NCLN	PGRMC1	psi-mi:“MI:0914”(association)	0.350
SCGB2A2	RTL8C	psi-mi:“MI:0914”(association)	0.350
NCLN	BFSP1	psi-mi:“MI:0914”(association)	0.350
CBLN4	NRXN2	psi-mi:“MI:0914”(association)	0.350

BioGRID (62): NOMO2 (Affinity Capture-RNA), NOMO2 (Affinity Capture-RNA), RPN1 (Co-fractionation), NOMO2 (Proximity Label-MS), NOMO2 (Affinity Capture-MS), NOMO2 (Affinity Capture-RNA), NOMO2 (Proximity Label-MS), NOMO2 (Positive Genetic), NOMO2 (Proximity Label-MS), NOMO2 (Proximity Label-MS), NOMO2 (Affinity Capture-MS), NOMO2 (Proximity Label-MS), NOMO2 (Proximity Label-MS), NOMO2 (Affinity Capture-MS), NOMO2 (Proximity Label-MS)

ESM2 similar proteins: A0A1D5PUP4, A2AFS3, M0R7X9, O70472, O75882, O95803, P01134, P26012, P52799, P52848, P69849, Q02353, Q05204, Q0VCJ8, Q12841, Q13635, Q15155, Q3UHN9, Q3ZBS2, Q58D84, Q5EA46, Q5JPE7, Q5R9Y1, Q5U4X8, Q5VV63, Q5ZJB7, Q5ZMH6, Q61115, Q62356, Q62632, Q6A051, Q6GQK9, Q6GQT9, Q6P988, Q6UXG2, Q7Z5A7, Q86TD4, Q90693, Q91WE9, Q96CW9

Diamond homologs: P69849, Q15155, Q5JPE7, Q6GQT9

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
NOMO2	“form complex”	“BOS complex, NOMO2 variant”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 43 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
SRP-dependent cotranslational protein targeting to membrane	6	23.1×	4e-05
Nonsense Mediated Decay (NMD) enhanced by the Exon Junction Complex (EJC)	5	18.8×	6e-04
Regulation of expression of SLITs and ROBOs	5	13.3×	1e-03
Translation	5	11.9×	1e-03

GO biological processes:

GO term	Partners	Fold	FDR
cytoplasmic translation	6	28.5×	3e-05

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	108
Likely benign	5
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

4061 predictions. Top by Δscore:

Variant	Effect	Δscore
16:18417965:TGAG:T	acceptor_gain	1.0000
16:18417966:GAG:G	acceptor_gain	1.0000
16:18418386:TCCTA:T	donor_loss	1.0000
16:18418387:CCTA:C	donor_loss	1.0000
16:18418388:CTA:C	donor_loss	1.0000
16:18418389:TA:T	donor_loss	1.0000
16:18418390:ACCT:A	donor_loss	1.0000
16:18418483:CT:C	acceptor_gain	1.0000
16:18418485:C:CC	acceptor_gain	1.0000
16:18429003:GACTT:G	donor_loss	1.0000
16:18429004:ACTTA:A	donor_loss	1.0000
16:18429005:CTT:C	donor_loss	1.0000
16:18429006:TTA:T	donor_loss	1.0000
16:18429007:T:TG	donor_loss	1.0000
16:18429008:A:AC	donor_gain	1.0000
16:18429008:AC:A	donor_gain	1.0000
16:18429008:ACC:A	donor_gain	1.0000
16:18429008:ACCCA:A	donor_loss	1.0000
16:18429009:C:CT	donor_gain	1.0000
16:18429009:CC:C	donor_gain	1.0000
16:18429009:CCC:C	donor_gain	1.0000
16:18429009:CCCAT:C	donor_gain	1.0000
16:18429116:CCAAC:C	acceptor_gain	1.0000
16:18429117:CAAC:C	acceptor_gain	1.0000
16:18429117:CAACC:C	acceptor_gain	1.0000
16:18429118:AAC:A	acceptor_gain	1.0000
16:18429119:AC:A	acceptor_gain	1.0000
16:18429119:ACCTA:A	acceptor_loss	1.0000
16:18429120:CC:C	acceptor_gain	1.0000
16:18429121:C:CC	acceptor_gain	1.0000

AlphaMissense

7972 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
16:18517190:A:G	L919P	1.000
16:18517238:C:G	R903P	1.000
16:18517256:A:G	L897P	1.000
16:18524516:A:C	F644C	1.000
16:18527552:A:G	C627R	1.000
16:18538941:G:C	F329L	1.000
16:18538941:G:T	F329L	1.000
16:18538943:A:G	F329L	1.000
16:18543684:A:T	V223D	1.000
16:18551458:C:T	G128E	1.000
16:18551459:C:A	G128W	1.000
16:18551494:C:T	C116Y	1.000
16:18551495:A:G	C116R	1.000
16:18554816:A:G	W98R	1.000
16:18554816:A:T	W98R	1.000
16:18557730:C:A	G76V	1.000
16:18557730:C:T	G76D	1.000
16:18557731:C:G	G76R	1.000
16:18557744:A:C	C71W	1.000
16:18557784:A:G	L58P	1.000
16:18561913:A:T	V43D	1.000
16:18561915:G:C	F42L	1.000
16:18561915:G:T	F42L	1.000
16:18561917:A:G	F42L	1.000
16:18561919:C:T	G41D	1.000
16:18561920:C:G	G41R	1.000
16:18514346:A:G	L1008S	0.999
16:18517252:A:C	S898R	0.999
16:18517252:A:T	S898R	0.999
16:18517254:T:G	S898R	0.999

dbSNP variants (sampled 300 via entrez): RS1000199060 (16:18539057 T>A,C,G), RS1000208225 (16:18551077 G>A), RS1000352422 (16:18529165 A>T), RS1000469591 (16:18560439 A>C,G), RS1000517727 (16:18553896 T>C), RS1000548862 (16:18553524 G>A), RS1000572061 (16:18553047 G>A,T), RS1000758662 (16:18542447 T>A), RS1000814840 (16:18539424 C>T), RS1000939913 (16:18541137 C>A,T), RS1000983189 (16:18532406 C>T), RS1001213253 (16:18524082 A>C), RS1001320034 (16:18534986 T>C), RS1001485207 (16:18525303 G>A), RS1002113425 (16:18562781 A>G)

Disease associations

OMIM: gene MIM:609158 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST008810_3	Smoking initiation (ever regular vs never regular)	3.000000e-10

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0005670	smoking initiation

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
2,4,6-tribromophenol	decreases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	decreases expression	1
decabromobiphenyl ether	increases expression	1
beta-lapachone	decreases expression	1
beta-methylcholine	affects expression	1
perfluorooctane sulfonic acid	increases expression	1
CGP 52608	affects binding, increases reaction	1
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	1
pentabrominated diphenyl ether 100	increases expression	1
Arsenic	affects methylation	1
Estradiol	increases expression	1
Tobacco Smoke Pollution	affects expression	1
Vitamin E	increases expression	1

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B1YR	Abcam HeLa NOMO2 KO	Cancer cell line	Female

Clinical trials (associated diseases)

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