SMIM14

Summary

SMIM14 (small integral membrane protein 14, HGNC:27321) is a protein-coding gene on chromosome 4p14, encoding Small integral membrane protein 14 (Q96QK8).

Predicted to act upstream of or within blastocyst hatching. Located in endoplasmic reticulum.

Source: NCBI Gene 201895 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 20 total
• MANE Select transcript: NM_174921

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:27321
Approved symbol	SMIM14
Name	small integral membrane protein 14
Location	4p14
Locus type	gene with protein product
Status	Approved
Aliases	FLJ13289
Ensembl gene	ENSG00000163683
Ensembl biotype	protein_coding
Entrez	201895

Gene structure

Transcript identifiers

Ensembl transcripts: 48 — 44 protein_coding, 3 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000295958, ENST00000505729, ENST00000507613, ENST00000510628, ENST00000511809, ENST00000512441, ENST00000630374, ENST00000865444, ENST00000865445, ENST00000865446, ENST00000865447, ENST00000865448, ENST00000865449, ENST00000865450, ENST00000865451, ENST00000865452, ENST00000865453, ENST00000865454, ENST00000865455, ENST00000865456, ENST00000865457, ENST00000865458, ENST00000865459, ENST00000865460, ENST00000865461, ENST00000865462, ENST00000865463, ENST00000865464, ENST00000865465, ENST00000865466, ENST00000865467, ENST00000865468, ENST00000865469, ENST00000865470, ENST00000865471, ENST00000865472, ENST00000865473, ENST00000938532, ENST00000938533, ENST00000938534, ENST00000938535, ENST00000938536, ENST00000938537, ENST00000942515, ENST00000942516, ENST00000942517, ENST00000942518, ENST00000942519

RefSeq mRNA: 3 — MANE Select: NM_174921 NM_001317896, NM_001317897, NM_174921

CCDS: CCDS3456

Canonical transcript exons

ENST00000295958 — 5 exons

Exon	Start	End
ENSE00001123004	39605071	39605180
ENSE00001207916	39546336	39552158
ENSE00002059210	39638739	39638865
ENSE00003608987	39572415	39572463
ENSE00003617936	39556428	39556570

Expression profiles

Bgee: expression breadth ubiquitous, 264 present calls, max score 99.14.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 32.2517 / max 378.2128, expressed in 1775 samples.

FANTOM5 promoters (9 alternative TSS)

Promoter ID	TPM avg	Samples expressed
51859	22.9262	1750
51863	2.4377	1190
51862	2.2790	1000
51857	1.2204	93
51860	1.1921	776
51864	0.8075	507
51865	0.5825	330
51866	0.5075	225
51861	0.2986	142

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
corpus epididymis	UBERON:0004359	99.14	gold quality
oviduct epithelium	UBERON:0004804	98.83	gold quality
caput epididymis	UBERON:0004358	98.69	gold quality
sperm	CL:0000019	98.62	gold quality
ileal mucosa	UBERON:0000331	98.41	gold quality
epithelial cell of pancreas	CL:0000083	98.36	gold quality
synovial joint	UBERON:0002217	98.36	gold quality
bronchial epithelial cell	CL:0002328	98.32	gold quality
bronchus	UBERON:0002185	98.28	gold quality
upper arm skin	UBERON:0004263	98.27	gold quality
epithelium of nasopharynx	UBERON:0001951	98.16	gold quality
nasopharynx	UBERON:0001728	98.15	gold quality
tendon of biceps brachii	UBERON:0008188	97.99	gold quality
gingival epithelium	UBERON:0001949	97.90	gold quality
palpebral conjunctiva	UBERON:0001812	97.88	gold quality
layer of synovial tissue	UBERON:0007616	97.87	gold quality
epithelium of mammary gland	UBERON:0003244	97.80	gold quality
mammary duct	UBERON:0001765	97.79	gold quality
trachea	UBERON:0003126	97.69	gold quality
kidney epithelium	UBERON:0004819	97.68	gold quality
cauda epididymis	UBERON:0004360	97.64	gold quality
germinal epithelium of ovary	UBERON:0001304	97.58	gold quality
lower lobe of lung	UBERON:0008949	97.57	gold quality
decidua	UBERON:0002450	97.45	gold quality
nasal cavity epithelium	UBERON:0005384	97.40	gold quality
esophagus squamous epithelium	UBERON:0006920	97.35	gold quality
liver	UBERON:0002107	97.31	gold quality
amniotic fluid	UBERON:0000173	97.30	gold quality
gingiva	UBERON:0001828	97.30	gold quality
mucosa of paranasal sinus	UBERON:0005030	97.29	gold quality

Single-cell (SCXA)

Detected in 14 experiment(s), a significant marker in 9.

Experiment	Marker?	Max mean expression
E-CURD-122	yes	106.32
E-HCAD-1	yes	103.13
E-CURD-88	yes	55.94
E-CURD-114	yes	43.99
E-CURD-46	yes	42.03
E-GEOD-125970	yes	26.47
E-MTAB-8142	yes	17.16
E-CURD-112	yes	14.53
E-HCAD-32	no	527.29
E-HCAD-6	no	293.72
E-CURD-97	no	176.89
E-MTAB-5061	no	4.07
E-HCAD-31	no	2.19
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

205 targeting SMIM14, 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-6833-3P	100.00	70.63	3197
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-4283	100.00	66.42	2097
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-188-3P	100.00	68.76	1240
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-4481	100.00	66.42	1669
HSA-MIR-150-5P	99.99	66.69	1976
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-539-3P	99.98	70.74	1616
HSA-MIR-485-3P	99.98	70.68	1585
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-302E	99.96	70.74	2669
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-570-3P	99.96	72.41	4910

Literature-anchored findings (GeneRIF, showing 1)

• hC4orf34 is an endoplasmic reticulum-resident type I transmembrane protein. (PMID:24499674)

Cross-species orthologs

27 orthologs

Organism	Symbol	Gene ID
danio_rerio	smim14	ENSDARG00000005799
mus_musculus	Smim14	ENSMUSG00000037822
rattus_norvegicus		ENSRNOG00000072377
rattus_norvegicus		ENSRNOG00000072620
rattus_norvegicus		ENSRNOG00000072722
rattus_norvegicus		ENSRNOG00000072900
rattus_norvegicus		ENSRNOG00000073657
rattus_norvegicus		ENSRNOG00000073932
rattus_norvegicus		ENSRNOG00000074772
rattus_norvegicus		ENSRNOG00000075496
rattus_norvegicus		ENSRNOG00000077197
rattus_norvegicus		ENSRNOG00000077602
rattus_norvegicus		ENSRNOG00000078662
rattus_norvegicus		ENSRNOG00000080064
rattus_norvegicus		ENSRNOG00000081642
rattus_norvegicus		ENSRNOG00000082170
rattus_norvegicus		ENSRNOG00000082286
rattus_norvegicus		ENSRNOG00000083166
rattus_norvegicus		ENSRNOG00000083790
rattus_norvegicus		ENSRNOG00000084903
rattus_norvegicus		ENSRNOG00000086287
rattus_norvegicus		ENSRNOG00000087828
rattus_norvegicus		ENSRNOG00000090331
rattus_norvegicus		ENSRNOG00000090629
rattus_norvegicus		ENSRNOG00000091003
drosophila_melanogaster	CG13585	FBGN0035020
caenorhabditis_elegans		WBGENE00007923

Protein

Protein identifiers

Small integral membrane protein 14 — Q96QK8 (reviewed: Q96QK8)

All UniProt accessions (4): D6R9U3, D6RDB1, Q96QK8, D6RGZ0

UniProt curated annotations — full annotation on UniProt →

Subcellular location. Endoplasmic reticulum membrane.

RefSeq proteins (3): NP_001304825, NP_001304826, NP_777581* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR020309	Smim-14	Family

Pfam: PF11027

UniProt features (7 total): topological domain 2, mutagenesis site 2, chain 1, transmembrane region 1, region of interest 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96QK8-F1	63.36	0.08

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 (2):

Position	Phenotype
26–27	in n-gly,n; creates a n-glycosylation site.
76–77	in n-gly,c; does not create a n-glycosylation site.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 240 (showing top): GOBP_EMBRYO_DEVELOPMENT_ENDING_IN_BIRTH_OR_EGG_HATCHING, GOZGIT_ESR1_TARGETS_DN, GOBP_IN_UTERO_EMBRYONIC_DEVELOPMENT, WANG_LMO4_TARGETS_DN, GOBP_BLASTOCYST_DEVELOPMENT, ACATTCC_MIR1_MIR206, CREIGHTON_ENDOCRINE_THERAPY_RESISTANCE_5, DOUGLAS_BMI1_TARGETS_DN, NAKAMURA_TUMOR_ZONE_PERIPHERAL_VS_CENTRAL_DN, TGTTTAC_MIR30A5P_MIR30C_MIR30D_MIR30B_MIR30E5P, FISCHER_DREAM_TARGETS, GOBP_EMBRYO_DEVELOPMENT, HAN_SATB1_TARGETS_DN, GRADE_COLON_AND_RECTAL_CANCER_DN, MILI_PSEUDOPODIA_CHEMOTAXIS_DN

GO Biological Process (1): blastocyst hatching (GO:0001835)

GO Molecular Function (1): protein binding (GO:0005515)

GO Cellular Component (3): endoplasmic reticulum (GO:0005783), endoplasmic reticulum membrane (GO:0005789), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
blastocyst development	1
hatching	1
binding	1
cytoplasm	1
endomembrane system	1
intracellular membrane-bounded organelle	1
organelle membrane	1
nuclear outer membrane-endoplasmic reticulum membrane network	1
endoplasmic reticulum subcompartment	1
cellular anatomical structure	1

Protein interactions and networks

STRING

548 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SMIM14	LIAS	O43766	571
SMIM14	TIGD4	Q8IY51	559
SMIM14	CNPPD1	Q9BV87	546
SMIM14	TMEM131L	A2VDJ0	540
SMIM14	TMEM156	Q8N614	508
SMIM14	COMMD8	Q9NX08	507
SMIM14	RFC1	P35251	498
SMIM14	RNF150	Q9ULK6	497
SMIM14	OCIAD2	Q56VL3	489
SMIM14	ARFIP1	P53367	475
SMIM14	TTC19	Q6DKK2	466
SMIM14	RBM47	A0AV96	451
SMIM14	PDS5A	Q29RF7	448
SMIM14	RCC1L	Q96I51	447
SMIM14	SYNPO2	Q9UMS6	438

IntAct

18 interactions, top by confidence:

A	B	Type	Score
FATE1	SMIM14	psi-mi:“MI:0915”(physical association)	0.670
SGTA	SMIM14	psi-mi:“MI:0915”(physical association)	0.560
TMEM42	SMIM14	psi-mi:“MI:0915”(physical association)	0.560
SLPI	SMIM14	psi-mi:“MI:0915”(physical association)	0.560
SMIM14	SPRED1	psi-mi:“MI:0915”(physical association)	0.560
SMIM14	FATE1	psi-mi:“MI:0915”(physical association)	0.000
SMIM14	SGTA	psi-mi:“MI:0915”(physical association)	0.000
TMEM42	SMIM14	psi-mi:“MI:0915”(physical association)	0.000
SMIM14	SLPI	psi-mi:“MI:0915”(physical association)	0.000
LSM4	SMIM14	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (7): FATE1 (Two-hybrid), SMIM14 (Two-hybrid), SMIM14 (Two-hybrid), SMIM14 (Two-hybrid), TMEM42 (Two-hybrid), SMIM14 (Affinity Capture-RNA), SMIM14 (Two-hybrid)

ESM2 similar proteins: A0A1B0GRQ0, A0A1B0GSZ0, A0A1B0GVT2, A0A590UK83, A0PK05, A2VDU1, A2VE22, A4QNL6, A5D7B5, A5D992, O43609, O75324, P0DKX4, P29414, P61807, P61808, Q0VFM5, Q15053, Q16655, Q17Q87, Q1L0X2, Q2KIK3, Q2TBG9, Q3MHM8, Q498C7, Q4V921, Q58CU5, Q5RBD8, Q5RF07, Q5RGQ8, Q64448, Q6UWT2, Q80ZU4, Q8BGN6, Q8BUM6, Q8C3K5, Q8C817, Q8K1D8, Q8N6S5, Q91VT8

Diamond homologs: Q09269, Q2KIK3, Q498C7, Q5RF07, Q91VT8, Q96QK8

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	12
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1471 predictions. Top by Δscore:

Variant	Effect	Δscore
4:39552059:A:AC	donor_gain	1.0000
4:39552060:C:CC	donor_gain	1.0000
4:39552060:CT:C	donor_gain	1.0000
4:39552111:T:TA	donor_gain	1.0000
4:39552112:C:A	donor_gain	1.0000
4:39556423:CTTAC:C	donor_loss	1.0000
4:39556424:TTA:T	donor_loss	1.0000
4:39556425:T:TG	donor_loss	1.0000
4:39556426:A:AC	donor_gain	1.0000
4:39556426:ACATT:A	donor_loss	1.0000
4:39556427:C:CC	donor_gain	1.0000
4:39556427:CA:C	donor_gain	1.0000
4:39556427:CAT:C	donor_gain	1.0000
4:39556427:CATT:C	donor_gain	1.0000
4:39556427:CATTA:C	donor_gain	1.0000
4:39556566:CGGTA:C	acceptor_gain	1.0000
4:39556567:GGTA:G	acceptor_gain	1.0000
4:39556568:GTA:G	acceptor_gain	1.0000
4:39556569:TA:T	acceptor_gain	1.0000
4:39556571:C:CC	acceptor_gain	1.0000
4:39556572:T:C	acceptor_loss	1.0000
4:39572464:C:CC	acceptor_gain	1.0000
4:39605055:T:TA	donor_gain	1.0000
4:39638815:T:TA	donor_gain	1.0000
4:39552072:T:TA	donor_gain	0.9900
4:39552165:T:TC	acceptor_gain	0.9900
4:39572413:A:AC	donor_gain	0.9900
4:39572413:ACATT:A	donor_gain	0.9900
4:39572414:C:CC	donor_gain	0.9900
4:39572414:CATT:C	donor_gain	0.9900

AlphaMissense

638 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
4:39556517:A:G	W60R	0.999
4:39556517:A:T	W60R	0.999
4:39572441:C:G	C33S	0.999
4:39572442:A:T	C33S	0.999
4:39572440:G:C	C33W	0.998
4:39572441:C:T	C33Y	0.998
4:39572442:A:G	C33R	0.998
4:39605081:A:G	L22P	0.998
4:39572426:C:G	C38S	0.997
4:39572427:A:G	C38R	0.997
4:39572427:A:T	C38S	0.997
4:39572441:C:A	C33F	0.997
4:39572462:A:G	L26S	0.997
4:39605072:A:G	L25P	0.997
4:39605120:C:T	C9Y	0.997
4:39572459:C:G	R27P	0.996
4:39556504:G:T	A64E	0.995
4:39572425:A:C	C38W	0.995
4:39605120:C:G	C9S	0.995
4:39605121:A:T	C9S	0.995
4:39605121:A:G	C9R	0.994
4:39605119:A:C	C9W	0.993
4:39605120:C:A	C9F	0.993
4:39572454:A:G	S29P	0.992
4:39605081:A:T	L22Q	0.992
4:39572426:C:T	C38Y	0.991
4:39572442:A:C	C33G	0.991
4:39605115:A:G	C11R	0.990
4:39572426:C:A	C38F	0.988
4:39605128:A:C	F6L	0.988

dbSNP variants (sampled 300 via entrez): RS1000003913 (4:39545966 A>G), RS1000013776 (4:39622054 A>G), RS1000029840 (4:39609134 G>A,C), RS1000082002 (4:39608788 A>G), RS1000115607 (4:39628944 G>T), RS1000180778 (4:39615991 A>G), RS1000215218 (4:39582422 T>C), RS1000305755 (4:39615102 T>G), RS1000319693 (4:39589367 A>G), RS1000322692 (4:39635120 C>T), RS10003596 (4:39582892 C>T), RS1000365151 (4:39549719 A>G), RS1000378048 (4:39597804 T>C), RS10004518 (4:39571301 G>A), RS1000462433 (4:39597539 G>A)

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

1 associations (top):

Study	Trait	p-value
GCST010244_77	Triglyceride levels	2.000000e-09

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004530	triglyceride measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, decreases expression, affects expression	5
Benzo(a)pyrene	increases expression, decreases expression	4
Cyclosporine	increases expression	4
trichostatin A	affects cotreatment, decreases expression	3
sodium arsenite	decreases expression, increases expression	2
(+)-JQ1 compound	increases expression	2
Cisplatin	affects expression, affects cotreatment, increases expression	2
Tunicamycin	increases expression	2
Aflatoxin B1	affects expression, decreases expression, decreases methylation	2
Cadmium Chloride	increases expression	2
p-Chloromercuribenzoic Acid	affects cotreatment, decreases expression	2
aristolochic acid I	increases expression	1
GSK-J4	decreases expression	1
afuresertib	increases expression	1
dicrotophos	decreases expression	1
alpha phellandrene	increases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	affects cotreatment, increases expression	1
manganese chloride	increases expression	1
dinophysistoxin 1	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	increases expression	1
apicidin	increases expression	1
K 7174	increases expression	1
scriptaid	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
erucylphospho-N,N,N-trimethylpropylammonium	increases expression	1
ICG 001	increases expression	1
abrine	decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1

Clinical trials (associated diseases)

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