BNIP1

Summary

BNIP1 (BCL2 interacting protein 1, HGNC:1082) is a protein-coding gene on chromosome 5q35.1, encoding Vesicle transport protein SEC20 (Q12981). As part of a SNARE complex may be involved in endoplasmic reticulum membranes fusion and be required for the maintenance of endoplasmic reticulum organization. It is a selective cancer dependency (DepMap: 50.1% of cell lines).

This gene is a member of the BCL2/adenovirus E1B 19 kd-interacting protein (BNIP) family. It interacts with the E1B 19 kDa protein, which protects cells from virally-induced cell death. The encoded protein also interacts with E1B 19 kDa-like sequences of BCL2, another apoptotic protector. In addition, this protein is involved in vesicle transport into the endoplasmic reticulum. Alternative splicing of this gene results in four protein products with identical N- and C-termini.

Source: NCBI Gene 662 — RefSeq curated summary.

At a glance

• Gene–disease (curated): spondyloepimetaphyseal dysplasia (Moderate, GenCC)
• GWAS associations: 6
• Clinical variants (ClinVar): 66 total — 1 pathogenic
• Phenotypes (HPO): 29
• Cancer dependency (DepMap): dependent in 50.1% of screened cell lines
• MANE Select transcript: NM_001205

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:1082
Approved symbol	BNIP1
Name	BCL2 interacting protein 1
Location	5q35.1
Locus type	gene with protein product
Status	Approved
Aliases	Nip1, SEC20
Ensembl gene	ENSG00000113734
Ensembl biotype	protein_coding
OMIM	603291
Entrez	662

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 8 protein_coding

ENST00000231668, ENST00000351486, ENST00000352523, ENST00000393770, ENST00000519459, ENST00000867149, ENST00000867150, ENST00000924880

RefSeq mRNA: 4 — MANE Select: NM_001205 NM_001205, NM_013978, NM_013979, NM_013980

CCDS: CCDS43400, CCDS4384, CCDS4385, CCDS4386

Canonical transcript exons

ENST00000351486 — 6 exons

Exon	Start	End
ENSE00000812890	173144531	173144629
ENSE00000812892	173146866	173146958
ENSE00000812896	173154322	173154413
ENSE00000812899	173158744	173158845
ENSE00000812901	173159933	173160051
ENSE00001616914	173163725	173164387

Expression profiles

Bgee: expression breadth ubiquitous, 226 present calls, max score 94.59.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 11.5171 / max 51.5767, expressed in 1791 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
60288	11.5171	1791

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
secondary oocyte	CL:0000655	94.59	gold quality
oocyte	CL:0000023	94.23	gold quality
diaphragm	UBERON:0001103	86.75	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	86.67	gold quality
mucosa of transverse colon	UBERON:0004991	85.91	gold quality
islet of Langerhans	UBERON:0000006	85.84	gold quality
right adrenal gland cortex	UBERON:0035827	83.87	gold quality
ventricular zone	UBERON:0003053	83.81	gold quality
right adrenal gland	UBERON:0001233	83.65	gold quality
body of pancreas	UBERON:0001150	83.60	gold quality
ganglionic eminence	UBERON:0004023	83.57	gold quality
pancreas	UBERON:0001264	83.53	gold quality
gastrocnemius	UBERON:0001388	83.29	gold quality
left adrenal gland	UBERON:0001234	83.23	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	83.20	gold quality
type B pancreatic cell	CL:0000169	82.90	gold quality
left adrenal gland cortex	UBERON:0035825	82.88	gold quality
muscle of leg	UBERON:0001383	82.85	gold quality
stromal cell of endometrium	CL:0002255	82.80	gold quality
olfactory bulb	UBERON:0002264	82.65	gold quality
apex of heart	UBERON:0002098	82.39	gold quality
adenohypophysis	UBERON:0002196	82.31	gold quality
adrenal cortex	UBERON:0001235	82.18	gold quality
hindlimb stylopod muscle	UBERON:0004252	82.11	gold quality
prefrontal cortex	UBERON:0000451	82.03	gold quality
heart left ventricle	UBERON:0002084	81.92	gold quality
right atrium auricular region	UBERON:0006631	81.81	gold quality
rectum	UBERON:0001052	81.78	gold quality
cortical plate	UBERON:0005343	81.68	gold quality
adrenal gland	UBERON:0002369	81.60	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	6.03

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

22 targeting BNIP1, 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-4482-3P	99.98	72.50	3147
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-MIR-1236-3P	99.94	68.04	1695
HSA-MIR-8063	99.91	69.76	3146
HSA-MIR-3151-5P	99.86	63.83	1069
HSA-MIR-24-3P	99.59	69.97	1934
HSA-MIR-4254	99.11	65.15	1315
HSA-MIR-6830-5P	99.01	68.73	1884
HSA-MIR-760	98.81	66.65	1392
HSA-MIR-548Q	98.71	65.35	563
HSA-MIR-561-5P	98.25	68.13	1365
HSA-MIR-503-5P	97.87	66.83	575
HSA-MIR-4799-3P	97.78	65.97	893
HSA-MIR-4720-5P	97.46	65.67	893
HSA-MIR-5588-5P	97.46	65.70	913
HSA-MIR-4640-5P	97.42	66.33	1543
HSA-MIR-4726-5P	97.24	65.67	1299
HSA-MIR-3126-3P	97.17	66.51	468
HSA-MIR-644A	96.02	66.52	786
HSA-MIR-6746-5P	92.37	63.66	103
HSA-MIR-6090	91.01	62.65	222

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 50.1% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 7)

• soluble N-ethylmaleimide-sensitive factor attachment protein may suppress apoptosis by competing with antiapoptotic proteins for the BH3 domain of BNIP1 (PMID:15272311)
• Human BNIP1 colocalizes with RNF185 at mitochondria and is polyubiquitinated by RNF185 through K63-based ubiquitin linkage in vivo. (PMID:21931693)
• ER-specific BNIP1 plays an important role in mitochondrial dynamics by modulating the mitochondrial fission protein Drp1 (PMID:22020994)
• three members of the BNIP family, BNIP1, BNIP3 and BNIP3L, are expressed in the developing brain with distinct brain region specificity (PMID:22639046)
• BNip1 functions as a downstream modulator of RNF186 to direct endoplasmic reticulum stress-associated apoptotic signaling. (PMID:23896122)
• The mitochondrial targeting domain (MTD) of Noxa has necrosis-inducing activity when conjugated with cell-penetrating peptide (CPP). In this study, we report another MTD-like motif, B1MLM, found in BNIP1, a pro-apoptotic BH3-only protein found in the endoplasmic reticulum membrane. The B1MLM peptide, conjugated with CPP, induced necrosis in a way similar to that of R8:MTD. (PMID:29222049)
• A homozygous hypomorphic BNIP1 variant causes an increase in autophagosomes and reduced autophagic flux and results in a spondylo-epiphyseal dysplasia. (PMID:35266227)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	bnip1a	ENSDARG00000078259
danio_rerio	bnip1b	ENSDARG00000104280
mus_musculus	Bnip1	ENSMUSG00000024191
rattus_norvegicus	Bnip1	ENSRNOG00000020753
drosophila_melanogaster	Sec20	FBGN0037383
caenorhabditis_elegans		WBGENE00018239

Protein

Protein identifiers

Vesicle transport protein SEC20 — Q12981 (reviewed: Q12981)

Alternative names: BCL2/adenovirus E1B 19 kDa protein-interacting protein 1, Transformation-related gene 8 protein

All UniProt accessions (2): Q12981, H0YBK7

UniProt curated annotations — full annotation on UniProt →

Function. As part of a SNARE complex may be involved in endoplasmic reticulum membranes fusion and be required for the maintenance of endoplasmic reticulum organization. Also plays a role in apoptosis. It is for instance required for endoplasmic reticulum stress-induced apoptosis. As a substrate of RNF185 interacting with SQSTM1, might also be involved in mitochondrial autophagy.

Subunit / interactions. Component of a SNARE complex consisting of STX18, USE1L, BNIP1/SEC20L and SEC22B. Interacts directly with STX18, RINT1/TIP20L and NAPA. Interacts with ZW10 through RINT1. Interacts with BCL2. Interacts with RNF186. Interacts with RNF185. Interacts with SQSTM1; increased by ‘Lys-63’-linked polyubiquitination of BNIP1. (Microbial infection) Interacts with adenovirus E1B 19K protein; plays a role in the suppression of cell apoptosis by the viral protein.

Subcellular location. Endoplasmic reticulum membrane. Mitochondrion membrane.

Tissue specificity. Isoform 1 is highly expressed in heart, brain, liver skeletal muscle and pancreas. Isoform 3 is moderately expressed in placenta, lung and kidney. Isoform 4 is highly expressed in testis and small intestine.

Post-translational modifications. Polyubiquitinated. ‘Lys-63’-linked polyubiquitination by RNF185 increases the interaction with the autophagy receptor SQSTM1. Undergoes ‘Lys-29’- and ‘Lys-63’-linked polyubiquitination by RNF186 that may regulate BNIP1 localization to the mitochondrion.

Disease relevance. Spondyloepiphyseal dysplasia, Holling type (SEDH) [MIM:621345] An autosomal recessive spondyloepiphyseal dysplasia characterized by disproportionate short stature and abnormalities of both the axial and the appendicular skeleton, primarily due to anomalies of the epiphyses. Mild metaphyseal irregularities are also observed. The disease may be caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the SEC20 family.

Isoforms (4)

UniProt ID	Names	Canonical?
Q12981-4	1, BNIP1, S4	yes
Q12981-2	2, BNIP1-a, S1
Q12981-1	3, BNIP1-b, S2
Q12981-3	4, BNIP1-c, S3

RefSeq proteins (4): NP_001196, NP_053581, NP_053582, NP_053583 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR005606	Sec20	Family
IPR056173	Sec20_C	Domain

Pfam: PF03908

UniProt features (12 total): sequence conflict 3, topological domain 2, splice variant 2, chain 1, transmembrane region 1, coiled-coil region 1, sequence variant 1, mutagenesis site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q12981-F1	80.86	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.

Mutagenesis-validated functional residues (1):

Position	Phenotype
114	loss of proapoptotic effect. no effect on interaction with rint1.

Function

Pathways and Gene Ontology

Reactome pathways

5 pathways

ID	Pathway
R-HSA-6811434	COPI-dependent Golgi-to-ER retrograde traffic
R-HSA-199991	Membrane Trafficking
R-HSA-5653656	Vesicle-mediated transport
R-HSA-6811442	Intra-Golgi and retrograde Golgi-to-ER traffic
R-HSA-8856688	Golgi-to-ER retrograde transport

MSigDB gene sets: 208 (showing top): MORF_FLT1, MORF_MSH3, STARK_PREFRONTAL_CORTEX_22Q11_DELETION_DN, MORF_BRCA1, GOBP_MEMBRANE_FUSION, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_DN, SABATES_COLORECTAL_ADENOMA_SIZE_DN, GOBP_VESICLE_MEDIATED_TRANSPORT, REACTOME_MEMBRANE_TRAFFICKING, MORF_ESR1, MORF_RAD51L3, GCM_MYCL1, GCM_RING1, GOBP_RESPONSE_TO_OXYGEN_LEVELS

GO Biological Process (12): retrograde vesicle-mediated transport, Golgi to endoplasmic reticulum (GO:0006890), apoptotic process (GO:0006915), endoplasmic reticulum organization (GO:0007029), response to activity (GO:0014823), endoplasmic reticulum membrane fusion (GO:0016320), response to starvation (GO:0042594), negative regulation of apoptotic process (GO:0043066), response to oxygen-glucose deprivation (GO:0090649), execution phase of apoptosis (GO:0097194), apoptotic process in response to mitochondrial fragmentation (GO:0140208), vesicle-mediated transport (GO:0016192), calcium-mediated signaling (GO:0019722)

GO Molecular Function (3): SNAP receptor activity (GO:0005484), calcium-induced calcium release activity (GO:0048763), protein binding (GO:0005515)

GO Cellular Component (11): nuclear envelope (GO:0005635), cytoplasm (GO:0005737), mitochondrial outer membrane (GO:0005741), endoplasmic reticulum (GO:0005783), endoplasmic reticulum membrane (GO:0005789), COPI-coated vesicle (GO:0030137), SNARE complex (GO:0031201), mitochondrial membrane (GO:0031966), intracellular membrane-bounded organelle (GO:0043231), mitochondrion (GO:0005739), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-4 pathways:

Category	Pathways
Golgi-to-ER retrograde transport	1
Vesicle-mediated transport	1
Membrane Trafficking	1
Intra-Golgi and retrograde Golgi-to-ER traffic	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
apoptotic process	3
cytoplasm	3
response to nutrient levels	2
cellular process	2
endomembrane system	2
intracellular anatomical structure	2
cellular anatomical structure	2
intracellular membrane-bounded organelle	2
organelle membrane	2
Golgi vesicle transport	1
programmed cell death	1
apoptotic signaling pathway	1
execution phase of apoptosis	1
organelle organization	1
endomembrane system organization	1
response to stimulus	1
endoplasmic reticulum organization	1
endoplasmic reticulum membrane organization	1
organelle membrane fusion	1
response to stress	1
regulation of apoptotic process	1
negative regulation of programmed cell death	1
response to decreased oxygen levels	1
bleb assembly	1
transport	1
intracellular signaling cassette	1
protein-macromolecule adaptor activity	1
membrane fusion	1
fusogenic activity	1
intracellularly gated calcium channel activity	1
binding	1
nucleus	1
organelle envelope	1
mitochondrial membrane	1
organelle outer membrane	1
nuclear outer membrane-endoplasmic reticulum membrane network	1
endoplasmic reticulum subcompartment	1
Golgi-associated vesicle	1
coated vesicle	1
membrane protein complex	1

Protein interactions and networks

STRING

1264 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
BNIP1	STX18	Q9P2W9	984
BNIP1	ZNF787	Q6DD87	953
BNIP1	BNIP2	Q12982	885
BNIP1	PIK3R4	Q99570	876
BNIP1	USE1	Q9NZ43	858
BNIP1	RINT1	Q6NUQ1	851
BNIP1	BNIP3	Q12983	837
BNIP1	BCL2	P10415	832
BNIP1	ATG14	Q6ZNE5	801
BNIP1	SEC22B	O75396	798
BNIP1	ZW10	O43264	780
BNIP1	GOSR2	O14653	726
BNIP1	BCL2L1	Q07817	706
BNIP1	YKT6	O15498	680
BNIP1	STX5	Q13190	666

IntAct

187 interactions, top by confidence:

A	B	Type	Score
RINT1	NBAS	psi-mi:“MI:0914”(association)	0.830
STX18	NBAS	psi-mi:“MI:0914”(association)	0.810
NAPA	SNAP23	psi-mi:“MI:0914”(association)	0.780
EXOC8	EXOC5	psi-mi:“MI:0914”(association)	0.730
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
STX6	GOSR2	psi-mi:“MI:0914”(association)	0.670
USE1	NBAS	psi-mi:“MI:0914”(association)	0.640
IFT57	IFT56	psi-mi:“MI:0914”(association)	0.640
ASPH	STXBP3	psi-mi:“MI:0914”(association)	0.640
BNIP1	NBAS	psi-mi:“MI:0914”(association)	0.640
NIPAL1	ESYT2	psi-mi:“MI:0914”(association)	0.640
STX7	SNAP23	psi-mi:“MI:0914”(association)	0.640
TEX28	TMCC2	psi-mi:“MI:0914”(association)	0.640

BioGRID (221): BNIP1 (Affinity Capture-MS), BNIP1 (Affinity Capture-MS), BNIP1 (Affinity Capture-MS), BNIP1 (Affinity Capture-MS), BNIP1 (Affinity Capture-MS), BNIP1 (Affinity Capture-MS), BNIP1 (Affinity Capture-MS), BNIP1 (Affinity Capture-MS), BNIP1 (Affinity Capture-MS), BNIP1 (Affinity Capture-MS), BNIP1 (Affinity Capture-MS), BNIP1 (Proximity Label-MS), BNIP1 (Affinity Capture-MS), BNIP1 (Affinity Capture-MS), BNIP1 (Affinity Capture-MS)

ESM2 similar proteins: A8XLW0, A8XP14, O04378, O13644, O14653, O35165, O35166, O65359, O89116, O94531, O94651, P25385, P38736, P41941, P59277, P78768, P93654, Q01590, Q04338, Q09835, Q12981, Q20797, Q39233, Q54CK6, Q54IX6, Q6BVM4, Q6BZQ6, Q6CRX0, Q6FKA1, Q6QD59, Q75CY3, Q8VHI8, Q95ZW1, Q96AJ9, Q9FFK1, Q9FK28, Q9HGN3, Q9JI51, Q9LK09, Q9LMP7

Diamond homologs: Q12981, Q6QD59, Q8VHI8

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
RNF185	“up-regulates activity”	BNIP1	polyubiquitination
BNIP1	“up-regulates activity”	SQSTM1	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 133 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
Intra-Golgi traffic	7	20.9×	3e-06
Retrograde transport at the Trans-Golgi-Network	6	15.2×	1e-04
COPII-mediated vesicle transport	6	11.2×	5e-04
Intra-Golgi and retrograde Golgi-to-ER traffic	9	10.8×	9e-06
COPI-dependent Golgi-to-ER retrograde traffic	7	8.9×	5e-04
ER to Golgi Anterograde Transport	5	7.6×	7e-03
Golgi-to-ER retrograde transport	5	7.6×	7e-03
Transport to the Golgi and subsequent modification	6	7.1×	4e-03

GO biological processes:

GO term	Partners	Fold	FDR
obsolete vesicle docking	8	52.4×	4e-10
vesicle fusion	10	51.4×	1e-12
membrane fusion	5	26.7×	1e-04
membrane depolarization	5	21.8×	3e-04
retrograde vesicle-mediated transport, Golgi to endoplasmic reticulum	6	17.3×	1e-04
monoatomic ion transmembrane transport	6	10.7×	1e-03
exocytosis	7	9.1×	9e-04
retrograde transport, endosome to Golgi	5	8.8×	9e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	49
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
1527205	GRCh37/hg19 5q34-35.1(chr5:164207156-172799124)	Pathogenic

SpliceAI

1179 predictions. Top by Δscore:

Variant	Effect	Δscore
5:173144628:AGGTA:A	donor_loss	1.0000
5:173144629:GGTAC:G	donor_loss	1.0000
5:173144630:G:GA	donor_loss	1.0000
5:173144631:T:A	donor_loss	1.0000
5:173154318:A:AG	acceptor_gain	1.0000
5:173154318:AAAG:A	acceptor_gain	1.0000
5:173154319:A:G	acceptor_gain	1.0000
5:173154319:AAGG:A	acceptor_loss	1.0000
5:173154320:A:C	acceptor_loss	1.0000
5:173154320:A:G	acceptor_gain	1.0000
5:173154321:G:GG	acceptor_gain	1.0000
5:173154321:G:GT	acceptor_loss	1.0000
5:173154382:G:GT	donor_gain	1.0000
5:173154409:CTCAG:C	donor_loss	1.0000
5:173154410:TCAG:T	donor_loss	1.0000
5:173154411:CAGGT:C	donor_loss	1.0000
5:173154412:AG:A	donor_loss	1.0000
5:173154413:GGTA:G	donor_loss	1.0000
5:173154414:G:T	donor_loss	1.0000
5:173154415:T:G	donor_loss	1.0000
5:173159922:T:TA	acceptor_gain	1.0000
5:173159925:A:AG	acceptor_gain	1.0000
5:173159926:C:G	acceptor_gain	1.0000
5:173159930:TA:T	acceptor_loss	1.0000
5:173159931:A:AG	acceptor_gain	1.0000
5:173159931:AG:A	acceptor_gain	1.0000
5:173159932:G:GA	acceptor_gain	1.0000
5:173159932:GG:G	acceptor_gain	1.0000
5:173159932:GGA:G	acceptor_gain	1.0000
5:173159932:GGAA:G	acceptor_gain	1.0000

AlphaMissense

1501 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
5:173163824:G:C	R197P	0.999
5:173163803:T:C	L190P	0.998
5:173163821:G:C	R196P	0.998
5:173163857:C:A	A208E	0.998
5:173163868:T:C	F212L	0.998
5:173163870:T:A	F212L	0.998
5:173163870:T:G	F212L	0.998
5:173163835:G:C	D201H	0.997
5:173163845:T:A	L204H	0.997
5:173158766:G:C	A98P	0.996
5:173163793:G:C	G187R	0.996
5:173163794:G:A	G187D	0.996
5:173163814:T:G	Y194D	0.996
5:173163836:A:C	D201A	0.996
5:173163845:T:C	L204P	0.996
5:173163878:C:A	T215K	0.996
5:173144607:T:C	L21P	0.995
5:173158773:T:C	L100P	0.995
5:173163836:A:T	D201V	0.995
5:173159986:T:C	L142P	0.994
5:173163842:T:C	L203P	0.994
5:173163814:T:C	Y194H	0.993
5:173163866:T:C	L211P	0.993
5:173163890:T:A	I219N	0.993
5:173163835:G:T	D201Y	0.992
5:173163845:T:G	L204R	0.992
5:173163878:C:G	T215R	0.992
5:173163797:G:C	R188P	0.991
5:173163803:T:A	L190H	0.991
5:173163869:T:C	F212S	0.991

dbSNP variants (sampled 300 via entrez): RS1000062343 (5:173144764 AC>A,ACC), RS1000115264 (5:173152034 C>A), RS1000119086 (5:173143766 G>C,T), RS1000153758 (5:173153313 T>C), RS1000436140 (5:173146191 A>G,T), RS1000547228 (5:173151372 C>A), RS1000721255 (5:173145119 T>C), RS1000785946 (5:173146614 A>G), RS1000973071 (5:173158653 G>A,C), RS1001136937 (5:173164272 A>G), RS1001438762 (5:173157758 C>A,T), RS1001570321 (5:173148587 G>A), RS1001579019 (5:173155676 G>A), RS1001814191 (5:173162163 T>C), RS1001837461 (5:173145526 T>C)

Disease associations

OMIM: gene MIM:603291 | disease phenotypes: MIM:183900, MIM:621345

GenCC curated gene-disease

Disease	Classification	Inheritance
spondyloepimetaphyseal dysplasia	Moderate	Autosomal recessive

Mondo (3): spondyloepiphyseal dysplasia congenita (MONDO:0008471), spondyloepiphyseal dysplasia, Holling type (MONDO:0979899), spondyloepimetaphyseal dysplasia (MONDO:0100510)

Orphanet (1): Spondyloepiphyseal dysplasia congenita (Orphanet:94068)

HPO phenotypes

29 total (29 of 29 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000348	High forehead
HP:0000767	Pectus excavatum
HP:0000774	Narrow chest
HP:0000926	Platyspondyly
HP:0001216	Delayed ossification of carpal bones
HP:0001270	Motor delay
HP:0001562	Oligohydramnios
HP:0002857	Genu valgum
HP:0002866	Hypoplastic iliac wing
HP:0002979	Bowing of the legs
HP:0003021	Metaphyseal cupping
HP:0003180	Flat acetabular roof
HP:0003300	Ovoid vertebral bodies
HP:0003375	Narrow greater sciatic notch
HP:0003593	Infantile onset
HP:0004322	Short stature
HP:0004379	Abnormality of alkaline phosphatase level
HP:0005484	Secondary microcephaly
HP:0008785	Delayed ossification of pubic rami
HP:0008897	Postnatal growth retardation
HP:0010034	Short 1st metacarpal
HP:0010236	Small epiphyses of the phalanges of the hand
HP:0011731	Abnormality of circulating cortisol level
HP:0030352	Abnormal circulating insulin-like growth factor 1 concentration
HP:0034197	Third trimester onset
HP:0100511	Abnormality of vitamin D metabolism
HP:0100864	Short femoral neck
HP:0430135	Abnormal circulating hepatic transaminase concentration

GWAS associations

6 associations (top):

Study	Trait	p-value
GCST001399_3	Infantile hypertrophic pyloric stenosis	1.000000e-15
GCST006065_7	Glaucoma (primary open-angle)	4.000000e-08
GCST007045_5	PR interval	6.000000e-21
GCST007226_7	PR interval	5.000000e-12
GCST007269_260	Pulse pressure	1.000000e-08
GCST010321_139	PR interval	5.000000e-55

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004462	PR interval
EFO:0005763	pulse pressure measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C535788	Spondyloepiphyseal dysplasia, congenita (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

37 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol A	decreases expression, increases expression	2
Cyclosporine	increases expression	2
3-((6-(2-methoxyphenyl)pyrimidin-4-yl)amino)phenyl)methane sulfonamide	decreases expression	1
deoxynivalenol	increases expression	1
beta-lapachone	increases expression	1
o,p’-DDT	increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
sodium arsenite	increases expression	1
cobaltous chloride	increases expression	1
manganese chloride	decreases expression, increases abundance	1
pentabromodiphenyl ether	increases expression	1
cylindrospermopsin	increases expression	1
CGP 52608	affects binding, increases reaction	1
abrine	increases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	increases expression	1
jinfukang	decreases expression, increases reaction	1
(+)-JQ1 compound	decreases expression	1
Resveratrol	increases expression	1
Vorinostat	decreases expression	1
Leflunomide	increases expression	1
Acetaminophen	decreases expression	1
Antimycin A	increases expression	1
Camptothecin	increases expression	1
Cisplatin	increases reaction, decreases expression	1
Fluorouracil	increases expression	1
Manganese	increases abundance, decreases expression	1
Methyl Methanesulfonate	increases expression	1
Paraquat	decreases expression	1
Rotenone	decreases expression	1
Smoke	decreases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT05408715	Not specified	RECRUITING	A Natural History Study in Children With a Type II Collagen Disorder With Short Stature