NOMO1

Summary

NOMO1 (NODAL modulator 1, HGNC:30060) is a protein-coding gene on chromosome 16p13.11, encoding BOS complex subunit NOMO1 (Q15155). 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).

Source: NCBI Gene 23420 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 210 total — 1 likely-pathogenic
• MANE Select transcript: NM_014287

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:30060
Approved symbol	NOMO1
Name	NODAL modulator 1
Location	16p13.11
Locus type	gene with protein product
Status	Approved
Aliases	PM5
Ensembl gene	ENSG00000103512
Ensembl biotype	protein_coding
OMIM	609157
Entrez	23420

Gene structure

Transcript identifiers

Ensembl transcripts: 15 — 11 protein_coding, 2 protein_coding_CDS_not_defined, 2 retained_intron

ENST00000287667, ENST00000565655, ENST00000566720, ENST00000566823, ENST00000566883, ENST00000566917, ENST00000880310, ENST00000880311, ENST00000880312, ENST00000924491, ENST00000924492, ENST00000924493, ENST00000924494, ENST00000924495, ENST00000959860

RefSeq mRNA: 1 — MANE Select: NM_014287 NM_014287

CCDS: CCDS10556

Canonical transcript exons

ENST00000287667 — 31 exons

Exon	Start	End
ENSE00001597222	14875340	14875422
ENSE00001617019	14844674	14844774
ENSE00001624960	14846577	14846683
ENSE00001631262	14880015	14880142
ENSE00001631895	14863013	14863187
ENSE00001636090	14872234	14872329
ENSE00001646124	14871621	14871684
ENSE00001660826	14875036	14875254
ENSE00001665237	14881544	14881685
ENSE00001666415	14866555	14866691
ENSE00001681699	14838407	14838496
ENSE00001684490	14882594	14882677
ENSE00001706192	14884372	14884482
ENSE00001711681	14876664	14876790
ENSE00001714703	14864585	14864726
ENSE00001744306	14868548	14868635
ENSE00001744404	14876359	14876518
ENSE00001761192	14878721	14878834
ENSE00001778856	14865024	14865155
ENSE00001779084	14886761	14886862
ENSE00001784564	14889096	14889215
ENSE00001790229	14841362	14841407
ENSE00001863034	14895514	14896157
ENSE00001870604	14833721	14834016
ENSE00003548628	14857217	14857322
ENSE00003564136	14857505	14857655
ENSE00003588866	14853937	14854026
ENSE00003634653	14853467	14853604
ENSE00003658151	14848899	14848971
ENSE00003671735	14894998	14895090
ENSE00003671846	14852430	14852582

Expression profiles

Bgee: expression breadth ubiquitous, 137 present calls, max score 97.49.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.2795 / max 10.3185, expressed in 107 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
207772	0.2795	107

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
islet of Langerhans	UBERON:0000006	97.49	gold quality
superior frontal gyrus	UBERON:0002661	97.30	gold quality
body of pancreas	UBERON:0001150	97.24	gold quality
primary visual cortex	UBERON:0002436	97.08	gold quality
pancreas	UBERON:0001264	97.07	gold quality
stromal cell of endometrium	CL:0002255	96.93	gold quality
corpus callosum	UBERON:0002336	96.84	gold quality
nucleus accumbens	UBERON:0001882	96.26	gold quality
right atrium auricular region	UBERON:0006631	96.10	gold quality
Brodmann (1909) area 9	UBERON:0013540	96.07	gold quality
calcaneal tendon	UBERON:0003701	95.48	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	95.42	gold quality
hindlimb stylopod muscle	UBERON:0004252	95.36	gold quality
muscle of leg	UBERON:0001383	95.23	gold quality
gastrocnemius	UBERON:0001388	95.20	gold quality
right frontal lobe	UBERON:0002810	95.08	gold quality
caudate nucleus	UBERON:0001873	94.86	gold quality
right hemisphere of cerebellum	UBERON:0014890	94.80	gold quality
putamen	UBERON:0001874	94.66	gold quality
colonic epithelium	UBERON:0000397	94.60	gold quality
hypothalamus	UBERON:0001898	94.60	gold quality
muscle tissue	UBERON:0002385	94.58	gold quality
skeletal muscle tissue	UBERON:0001134	94.53	gold quality
heart	UBERON:0000948	94.50	gold quality
cerebral cortex	UBERON:0000956	94.44	gold quality
cerebellum	UBERON:0002037	94.44	gold quality
anterior cingulate cortex	UBERON:0009835	94.43	gold quality
frontal cortex	UBERON:0001870	94.41	gold quality
cerebellar cortex	UBERON:0002129	94.41	gold quality
cerebellar hemisphere	UBERON:0002245	94.32	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	7.22

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

18 targeting NOMO1, 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-3605-5P	99.96	67.12	932
HSA-MIR-3681-5P	99.82	66.88	387
HSA-MIR-2681-5P	99.75	67.64	1655
HSA-MIR-4719	99.73	72.10	3329
HSA-MIR-6849-5P	99.64	66.00	352
HSA-MIR-4291	99.20	68.88	2969
HSA-MIR-4478	99.07	65.16	2320
HSA-MIR-3619-5P	99.00	68.87	2308
HSA-MIR-214-3P	98.71	68.12	2128
HSA-MIR-761	98.71	68.07	2051
HSA-MIR-9500	98.62	66.54	1845
HSA-MIR-3929	98.32	65.58	1026
HSA-MIR-6841-3P	98.08	66.54	604
HSA-MIR-1245B-3P	98.01	68.91	1387
HSA-MIR-1912-5P	97.94	67.98	832
HSA-MIR-5194	96.77	63.91	1021
HSA-MIR-6508-3P	96.73	65.48	576
HSA-MIR-12115	94.19	66.37	738

Literature-anchored findings (GeneRIF, showing 2)

• H19 gene could inhibit human trophoblast cell proliferation via encoding miR-675 that targeted NOMO1 downregulation. (PMID:22832245)
• Microsatellite-Stable (MSS) CRC showed a very high proportion of homozygous loss of NOMO1 (54 of 59 cases, 91.5%), while the deletion was observed in only 7 out of 16 MSI cases. Deletion of NOMO1 is a molecular marker predominantly associated with CRC, particularly MSS subtypes. (PMID:28416736)

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), NOMO2 (ENSG00000185164)

Protein

Protein identifiers

BOS complex subunit NOMO1 — Q15155 (reviewed: Q15155)

Alternative names: Nodal modulator 1, pM5 protein

All UniProt accessions (2): Q15155, H3BUC9

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. Expressed in colon tumor tissue and in adjacent normal colonic mucosa.

RefSeq proteins (1): NP_055102* (*=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 (29 total): sequence variant 9, sequence conflict 9, glycosylation site 3, topological domain 2, signal peptide 1, chain 1, transmembrane region 1, region of interest 1, compositionally biased region 1, modified residue 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q15155-F1	81.61	0.29

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 (1): 1205

Glycosylation sites (3): 618, 50, 218

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 122 (showing top): KAAB_HEART_ATRIUM_VS_VENTRICLE_UP, RIZKI_TUMOR_INVASIVENESS_3D_DN, GOBP_SPECIFICATION_OF_SYMMETRY, GOBP_LATERAL_MESODERM_DEVELOPMENT, GOBP_REGULATION_OF_TRANSMEMBRANE_RECEPTOR_PROTEIN_SERINE_THREONINE_KINASE_SIGNALING_PATHWAY, GOBP_ESTABLISHMENT_OF_PROTEIN_LOCALIZATION_TO_MEMBRANE, GOBP_ENDOMEMBRANE_SYSTEM_ORGANIZATION, GOBP_ACTIVIN_RECEPTOR_SIGNALING_PATHWAY, GOBP_PROTEIN_LOCALIZATION_TO_ORGANELLE, GOBP_MESENCHYME_DEVELOPMENT, GOBP_MEMBRANE_ORGANIZATION, SASAKI_ADULT_T_CELL_LEUKEMIA, GOBP_ENDOPLASMIC_RETICULUM_ORGANIZATION, GOBP_MESODERM_DEVELOPMENT, GOBP_LOCALIZATION_WITHIN_MEMBRANE

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 (4): endoplasmic reticulum membrane (GO:0005789), membrane (GO:0016020), multi-pass translocon complex (GO:0160064), endoplasmic reticulum (GO:0005783)

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 anatomical structure	1
ER membrane insertion complex	1
cytoplasm	1
endomembrane system	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

0 interactions, top by confidence (×1000):

IntAct

177 interactions, top by confidence:

A	B	Type	Score
HS2ST1	SLC7A1	psi-mi:“MI:0914”(association)	0.730
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
B3GNT3	PGRMC1	psi-mi:“MI:0914”(association)	0.670
CSNK2B	RPS6KA4	psi-mi:“MI:0914”(association)	0.640
FBXO6	MAN2B1	psi-mi:“MI:0914”(association)	0.640
FBXO2	TMEM131L	psi-mi:“MI:0914”(association)	0.530
CD79A	METTL15	psi-mi:“MI:0914”(association)	0.530
TPCN2	AP3B1	psi-mi:“MI:0914”(association)	0.530
APOD	CCN1	psi-mi:“MI:0914”(association)	0.530
TNF	B4GALT5	psi-mi:“MI:0914”(association)	0.530
APLNR	SLC33A1	psi-mi:“MI:0914”(association)	0.530
NCEH1	CLGN	psi-mi:“MI:0914”(association)	0.530
SPCS3	ENTPD6	psi-mi:“MI:0914”(association)	0.530
UPF3B	NOMO1	psi-mi:“MI:0915”(physical association)	0.400
CYTH4	NOMO1	psi-mi:“MI:0915”(physical association)	0.400
ATRX	NOMO1	psi-mi:“MI:0915”(physical association)	0.400
EPHA2	NOMO1	psi-mi:“MI:0915”(physical association)	0.400
MYO9B	NOMO1	psi-mi:“MI:0915”(physical association)	0.400
MROH2A	NOMO1	psi-mi:“MI:0915”(physical association)	0.400
ZNF492	NOMO1	psi-mi:“MI:0915”(physical association)	0.400
	GNAT3	psi-mi:“MI:0915”(physical association)	0.400
PLA2G12B	NOMO1	psi-mi:“MI:0915”(physical association)	0.400
NOMO1	DLG4	psi-mi:“MI:0915”(physical association)	0.370
STAT1	NOMO1	psi-mi:“MI:0915”(physical association)	0.370
ATF7IP	NOMO1	psi-mi:“MI:0915”(physical association)	0.370
NOMO1	TRIM63	psi-mi:“MI:0915”(physical association)	0.370
NOMO1	SMURF2	psi-mi:“MI:0915”(physical association)	0.370

BioGRID (214): NOMO1 (Two-hybrid), NOMO1 (Two-hybrid), RPN1 (Co-fractionation), NOMO1 (Affinity Capture-MS), NOMO1 (Proximity Label-MS), NOMO1 (Affinity Capture-MS), NOMO1 (Affinity Capture-MS), NOMO1 (Affinity Capture-MS), NOMO1 (Affinity Capture-MS), NOMO1 (Affinity Capture-MS), NOMO1 (Affinity Capture-MS), METTL9 (Affinity Capture-MS), SERINC1 (Affinity Capture-MS), NOMO1 (Affinity Capture-MS), NOMO1 (Affinity Capture-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
NOMO1	“form complex”	“BOS complex, NOMO1 variant”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 239 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.

GO biological processes:

GO term	Partners	Fold	FDR
ERAD pathway	10	8.3×	5e-04
monoatomic ion transmembrane transport	8	7.7×	8e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	1
Uncertain significance	169
Likely benign	16
Benign	1

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
815802	GRCh37/hg19 16p13.11(chr16:14927857-15375547)x3	Likely pathogenic

SpliceAI

4209 predictions. Top by Δscore:

Variant	Effect	Δscore
16:14834013:CGAGG:C	donor_loss	1.0000
16:14834014:GAG:G	donor_gain	1.0000
16:14834014:GAGGT:G	donor_loss	1.0000
16:14834016:GGTG:G	donor_loss	1.0000
16:14834017:G:GA	donor_loss	1.0000
16:14834017:G:GG	donor_gain	1.0000
16:14834018:T:G	donor_loss	1.0000
16:14838402:TCCA:T	acceptor_loss	1.0000
16:14838404:CAGA:C	acceptor_loss	1.0000
16:14838405:A:AG	acceptor_gain	1.0000
16:14838406:G:GA	acceptor_gain	1.0000
16:14838406:G:GC	acceptor_loss	1.0000
16:14838406:GAT:G	acceptor_gain	1.0000
16:14838406:GATA:G	acceptor_gain	1.0000
16:14838406:GATAA:G	acceptor_gain	1.0000
16:14841358:TTA:T	acceptor_loss	1.0000
16:14841359:TA:T	acceptor_loss	1.0000
16:14841360:A:AG	acceptor_gain	1.0000
16:14841360:AG:A	acceptor_gain	1.0000
16:14841360:AGG:A	acceptor_gain	1.0000
16:14841360:AGGG:A	acceptor_gain	1.0000
16:14841360:AGGGG:A	acceptor_gain	1.0000
16:14841361:G:GG	acceptor_gain	1.0000
16:14841361:G:GT	acceptor_loss	1.0000
16:14841361:GG:G	acceptor_gain	1.0000
16:14841361:GGG:G	acceptor_gain	1.0000
16:14841361:GGGG:G	acceptor_gain	1.0000
16:14841361:GGGGG:G	acceptor_gain	1.0000
16:14841405:TTGG:T	donor_loss	1.0000
16:14841407:GGTA:G	donor_loss	1.0000

AlphaMissense

7983 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
16:14833966:T:C	C39R	1.000
16:14833972:G:C	G41R	1.000
16:14833973:G:A	G41D	1.000
16:14833975:T:C	F42L	1.000
16:14833977:C:A	F42L	1.000
16:14833977:C:G	F42L	1.000
16:14833979:T:A	V43D	1.000
16:14838414:T:C	L58P	1.000
16:14838467:G:C	G76R	1.000
16:14838467:G:T	G76C	1.000
16:14838468:G:A	G76D	1.000
16:14838468:G:T	G76V	1.000
16:14841398:T:A	W98R	1.000
16:14841398:T:C	W98R	1.000
16:14844718:T:A	C116S	1.000
16:14844718:T:C	C116R	1.000
16:14844719:G:A	C116Y	1.000
16:14844719:G:C	C116S	1.000
16:14844755:G:A	G128E	1.000
16:14857238:T:C	F329L	1.000
16:14857240:C:A	F329L	1.000
16:14857240:C:G	F329L	1.000
16:14878767:T:C	L897P	1.000
16:14878785:G:C	R903P	1.000
16:14878833:T:C	L919P	1.000
16:14833966:T:A	C39S	0.999
16:14833967:G:A	C39Y	0.999
16:14833967:G:C	C39S	0.999
16:14833968:C:G	C39W	0.999
16:14833972:G:T	G41C	0.999

dbSNP variants (sampled 300 via entrez): RS1000063660 (16:14841292 C>G), RS1000162126 (16:14864315 C>T), RS1000283793 (16:14872335 A>G), RS1000443565 (16:14864498 G>A), RS1000504416 (16:14847706 C>T), RS1000533886 (16:14847232 CAA>C), RS1000587524 (16:14857140 G>A), RS1000694638 (16:14895851 G>A), RS1000717527 (16:14873092 C>T), RS1000746996 (16:14894643 A>G), RS1000790928 (16:14856920 G>A,C), RS1000806763 (16:14848118 A>G,T), RS1000834228 (16:14887805 A>G), RS1000885987 (16:14832523 G>A,C), RS1001007967 (16:14880249 G>C)

Disease associations

OMIM: gene MIM:609157 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

24 total (human), top 24 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol F	increases expression, affects cotreatment, decreases expression	2
trichostatin A	affects expression, decreases reaction	2
FR900359	affects phosphorylation	1
triphenyl phosphate	affects expression	1
coumarin	decreases phosphorylation	1
CGP 52608	affects binding, increases reaction	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
ICG 001	decreases expression	1
bisphenol B	increases expression	1
bisphenol S	increases expression	1
LDN 193189	affects cotreatment, decreases expression	1
bisphenol AF	increases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	decreases expression	1
Dexamethasone	affects cotreatment, decreases expression	1
Estradiol	increases expression	1
Indomethacin	affects cotreatment, decreases expression	1
Lead	affects expression	1
Nickel	decreases reaction, affects expression	1
Ribonucleotides	affects binding	1
Theophylline	affects binding	1
Thiram	decreases expression	1
Tobacco Smoke Pollution	increases expression	1
1-Methyl-3-isobutylxanthine	affects cotreatment, decreases expression	1
Cadmium Chloride	decreases expression	1

Clinical trials (associated diseases)

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