YIPF5

Summary

YIPF5 (Yip1 domain family member 5, HGNC:24877) is a protein-coding gene on chromosome 5q31.3, encoding Protein YIPF5 (Q969M3). Plays a role in transport between endoplasmic reticulum and Golgi.

Involved in insulin processing and regulation of ER to Golgi vesicle-mediated transport. Located in Golgi apparatus; endoplasmic reticulum; and nucleoplasm.

Source: NCBI Gene 81555 — RefSeq curated summary.

At a glance

• Gene–disease (curated): microcephaly, epilepsy, and diabetes syndrome 2 (Strong, GenCC) — +1 more curated relationship
• GWAS associations: 2
• Clinical variants (ClinVar): 40 total — 2 pathogenic
• Phenotypes (HPO): 9
• Druggable target: yes
• MANE Select transcript: NM_030799

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:24877
Approved symbol	YIPF5
Name	Yip1 domain family member 5
Location	5q31.3
Locus type	gene with protein product
Status	Approved
Aliases	SMAP-5, FinGER5, Yip1a, YIPFalpha1A
Ensembl gene	ENSG00000145817
Ensembl biotype	protein_coding
OMIM	611483
Entrez	81555

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 6 protein_coding, 1 retained_intron

ENST00000274496, ENST00000448443, ENST00000508754, ENST00000513112, ENST00000519064, ENST00000522203, ENST00000956131

RefSeq mRNA: 3 — MANE Select: NM_030799 NM_001024947, NM_001271732, NM_030799

CCDS: CCDS4279, CCDS64277

Canonical transcript exons

ENST00000274496 — 6 exons

Exon	Start	End
ENSE00001895319	144170535	144170659
ENSE00001899266	144158162	144160559
ENSE00003476110	144164111	144164256
ENSE00003520495	144169846	144169965
ENSE00003522357	144162218	144162399
ENSE00003563357	144165432	144165604

Expression profiles

Bgee: expression breadth ubiquitous, 276 present calls, max score 97.55.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 59.2798 / max 1196.6290, expressed in 1822 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
63970	48.1583	1822
63969	10.9858	1574
203725	0.1357	48

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
jejunal mucosa	UBERON:0000399	97.55	gold quality
mucosa of paranasal sinus	UBERON:0005030	97.01	gold quality
stromal cell of endometrium	CL:0002255	96.96	gold quality
penis	UBERON:0000989	96.72	gold quality
corpus epididymis	UBERON:0004359	96.69	gold quality
synovial joint	UBERON:0002217	96.67	gold quality
decidua	UBERON:0002450	96.41	gold quality
mucosa of sigmoid colon	UBERON:0004993	96.32	gold quality
skin of hip	UBERON:0001554	96.04	gold quality
caput epididymis	UBERON:0004358	95.97	gold quality
colonic mucosa	UBERON:0000317	95.93	gold quality
oral cavity	UBERON:0000167	95.90	gold quality
islet of Langerhans	UBERON:0000006	95.62	gold quality
lower lobe of lung	UBERON:0008949	95.57	gold quality
bronchial epithelial cell	CL:0002328	95.55	gold quality
pylorus	UBERON:0001166	95.47	gold quality
upper leg skin	UBERON:0004262	95.40	gold quality
mammary duct	UBERON:0001765	95.35	gold quality
superior surface of tongue	UBERON:0007371	95.16	gold quality
cauda epididymis	UBERON:0004360	95.15	gold quality
pericardium	UBERON:0002407	95.05	gold quality
mammalian vulva	UBERON:0000997	95.01	gold quality
seminal vesicle	UBERON:0000998	94.72	gold quality
parotid gland	UBERON:0001831	94.54	gold quality
superficial temporal artery	UBERON:0001614	94.50	gold quality
oocyte	CL:0000023	94.34	gold quality
calcaneal tendon	UBERON:0003701	94.07	gold quality
buccal mucosa cell	CL:0002336	94.03	gold quality
jejunum	UBERON:0002115	94.03	gold quality
duodenum	UBERON:0002114	94.01	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

127 targeting YIPF5, 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-4795-3P	100.00	74.62	4024
HSA-MIR-450A-1-3P	100.00	69.33	1837
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-188-3P	100.00	68.76	1240
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-7152-3P	99.97	67.47	849
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-9-3P	99.96	70.88	2068
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-4666A-3P	99.96	71.71	3434
HSA-MIR-548AB	99.95	71.31	3488
HSA-MIR-559	99.95	72.28	3609
HSA-MIR-9983-3P	99.94	71.48	3631
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-548A-5P	99.94	71.27	3482
HSA-MIR-548AD-5P	99.94	71.23	3502
HSA-MIR-548AE-5P	99.94	71.23	3502
HSA-MIR-548AK	99.94	71.24	3488
HSA-MIR-548AM-5P	99.94	71.24	3488
HSA-MIR-548AP-5P	99.94	71.14	3489

Literature-anchored findings (GeneRIF, showing 12)

• The highest level of expression was found in coronary smooth muscle cells, in which expression of the SMAP-5 gene was induced by transforming growth factor beta1, thus indicating that this protein may play an important role in inflammation. (PMID:15922870)
• Human Yip1A (YIPF5) interacts with and localizes human Yif1 (YIF1A) to the Golgi apparatus. (PMID:15990086)
• YIPF5 is not restricted to Endoplasmic Reticulum exit sites but also localized in the ER-Golgi intermediate compartment (ERGIC) and some in the cis-Golgi at steady state (PMID:18718466)
• These results suggested that Yip1A has a role in COPI-independent retrograde transport from the Golgi to the ER and regulates the membrane recruitment of Rab6. (PMID:19509059)
• Results reveal a conserved Yip1A-mediated mechanism for ER membrane organization that may serve to regulate cargo exit from the organelle. (PMID:20237155)
• Findings suggest that the ability of Yip1A to bind its established binding partners may be uncoupled from its ability to control ER whorl formation. (PMID:23342155)
• we propose a model for intracellular Brucella replication that exploits the host unfolded protein response and endoplasmic reticulum -derived vacuole formation machineries, both of which depend on Yip1A-mediated IRE1 activation. (PMID:25742138)
• The significance of YIPF5 protein for the maintenance of the morphology of the Golgi was tested by RNA interference, revealing a number of specific morphological changes to this organelle on their depletion. (PMID:27999994)
• YIPF5 positively regulates STING-mediated innate immune responses. (PMID:31391232)
• YIPF5 mutations cause neonatal diabetes and microcephaly through endoplasmic reticulum stress. (PMID:33164986)
• Vitamin D receptor (VDR) mediates the quiescence of activated hepatic stellate cells (aHSCs) by regulating M2 macrophage exosomal smooth muscle cell-associated protein 5 (SMAP-5). (PMID:36916000)
• Balanced chromosomal rearrangements implicate YIPF5 and SPATC1L in non-obstructive oligoasthenozoospermia and oligozoospermia and of a derivative chromosome 22 in recurrent miscarriage. (PMID:37625567)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	yipf5	ENSDARG00000007279
mus_musculus	Yipf5	ENSMUSG00000024487
rattus_norvegicus	Yipf5	ENSRNOG00000014564
drosophila_melanogaster	Yip1d1	FBGN0032465
caenorhabditis_elegans		WBGENE00009336

Paralogs (3): YIPF4 (ENSG00000119820), YIPF7 (ENSG00000177752), YIPF6 (ENSG00000181704)

Protein

Protein identifiers

Protein YIPF5 — Q969M3 (reviewed: Q969M3)

Alternative names: Five-pass transmembrane protein localizing in the Golgi apparatus and the endoplasmic reticulum 5, Smooth muscle cell-associated protein 5, YIP1 family member 5, YPT-interacting protein 1 A

All UniProt accessions (3): E5RGR9, E5RHH4, Q969M3

UniProt curated annotations — full annotation on UniProt →

Function. Plays a role in transport between endoplasmic reticulum and Golgi. In pancreatic beta cells, required to transport proinsulin from endoplasmic reticulum into the Golgi.

Subunit / interactions. Interacts with the COPII coat components Sec23 (SEC23A and/or SEC23B) and Sec24 (SEC24A and/or SEC24B). Interacts with YIF1A. May interact with RAB1A. Interacts with YIPF3 and YIPF4.

Subcellular location. Endoplasmic reticulum membrane. Golgi apparatus. cis-Golgi network membrane. Cytoplasmic vesicle. COPII-coated vesicle.

Tissue specificity. Ubiquitously expressed with abundant expression in pancreatic tissue, islets, beta cells, and brain. Highly expressed in coronary smooth muscles.

Disease relevance. Microcephaly, epilepsy, and diabetes syndrome 2 (MEDS2) [MIM:619278] An autosomal recessive disorder characterized by neonatal or early-onset diabetes, severe microcephaly, and epilepsy. The disease is caused by variants affecting the gene represented in this entry.

Induction. By TGFB1.

Similarity. Belongs to the YIP1 family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q969M3-1	1	yes
Q969M3-2	2, D
Q969M3-3	3, I

RefSeq proteins (3): NP_001020118, NP_001258661, NP_110426* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR006977	Yip1_dom	Domain
IPR045231	Yip1/4-like	Family

Pfam: PF04893

UniProt features (24 total): topological domain 5, transmembrane region 5, sequence variant 5, sequence conflict 5, splice variant 2, chain 1, region of interest 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q969M3-F1	66.45	0.19

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 202 (showing top): RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, YAO_TEMPORAL_RESPONSE_TO_PROGESTERONE_CLUSTER_10, RODRIGUES_THYROID_CARCINOMA_POORLY_DIFFERENTIATED_UP, GOBP_VESICLE_ORGANIZATION, GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_UP, GOBP_MEMBRANE_FUSION, GOBP_REGULATION_OF_HORMONE_LEVELS, GNF2_PTX3, GAUSSMANN_MLL_AF4_FUSION_TARGETS_E_UP, GOBP_VESICLE_MEDIATED_TRANSPORT, GOBP_REGULATION_OF_VESICLE_MEDIATED_TRANSPORT, GOBP_PROTEIN_MATURATION, GOCC_TRANS_GOLGI_NETWORK, RICKMAN_TUMOR_DIFFERENTIATED_WELL_VS_POORLY_DN, GOBP_ENDOPLASMIC_RETICULUM_TO_GOLGI_VESICLE_MEDIATED_TRANSPORT

GO Biological Process (7): endoplasmic reticulum to Golgi vesicle-mediated transport (GO:0006888), protein transport (GO:0015031), insulin processing (GO:0030070), vesicle fusion with Golgi apparatus (GO:0048280), regulation of ER to Golgi vesicle-mediated transport (GO:0060628), Golgi organization (GO:0007030), vesicle-mediated transport (GO:0016192)

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

GO Cellular Component (12): nucleoplasm (GO:0005654), endoplasmic reticulum (GO:0005783), endoplasmic reticulum membrane (GO:0005789), Golgi apparatus (GO:0005794), trans-Golgi network (GO:0005802), COPII-coated ER to Golgi transport vesicle (GO:0030134), endoplasmic reticulum exit site (GO:0070971), Golgi membrane (GO:0000139), endomembrane system (GO:0012505), membrane (GO:0016020), cytoplasmic vesicle (GO:0031410), nuclear outer membrane-endoplasmic reticulum membrane network (GO:0042175)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cytoplasm	4
cellular anatomical structure	4
endomembrane system	3
Golgi vesicle transport	2
transport	2
intracellular membrane-bounded organelle	2
intercellular transport	1
intracellular transport	1
intracellular protein localization	1
establishment of protein localization	1
peptide hormone processing	1
insulin metabolic process	1
vesicle fusion	1
Golgi organization	1
endoplasmic reticulum to Golgi vesicle-mediated transport	1
regulation of intracellular transport	1
regulation of vesicle-mediated transport	1
organelle organization	1
endomembrane system organization	1
cellular process	1
binding	1
nuclear lumen	1
organelle membrane	1
nuclear outer membrane-endoplasmic reticulum membrane network	1
endoplasmic reticulum subcompartment	1
Golgi apparatus subcompartment	1
coated vesicle	1
endoplasmic reticulum	1
Golgi apparatus	1
bounding membrane of organelle	1
vacuole	1
plasma membrane	1
intracellular vesicle	1
membrane	1

Protein interactions and networks

STRING

1074 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
YIPF5	YIF1A	O95070	986
YIPF5	SEC24B	O95487	928
YIPF5	YIPF3	Q9GZM5	666
YIPF5	GOLPH3	Q9H4A6	654
YIPF5	YIPF6	Q96EC8	618
YIPF5	ERN1	O75460	610
YIPF5	YIF1B	Q5BJH7	584
YIPF5	RAB6A	P20340	579
YIPF5	IER3IP1	Q9Y5U9	570
YIPF5	YIPF2	Q9BWQ6	501
YIPF5	SEC13	P55735	470
YIPF5	YIPF1	Q9Y548	442
YIPF5	REEP6	Q96HR9	439
YIPF5	RAB1A	P11476	428
YIPF5	KIF5B	P33176	424

IntAct

78 interactions, top by confidence:

A	B	Type	Score
YIF1A	YIPF5	psi-mi:“MI:0915”(physical association)	0.790
YIF1A	YIPF5	psi-mi:“MI:0403”(colocalization)	0.790
PIGS	GPAA1	psi-mi:“MI:0914”(association)	0.760
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
PSMD14	PSMD11	psi-mi:“MI:0914”(association)	0.650
VAPB	YIF1A	psi-mi:“MI:0403”(colocalization)	0.600
ERN1	YIPF5	psi-mi:“MI:0915”(physical association)	0.540
ERN1	YIPF5	psi-mi:“MI:0403”(colocalization)	0.540
CD63	LGALS8	psi-mi:“MI:0914”(association)	0.530
FLVCR1	TNFRSF10B	psi-mi:“MI:0914”(association)	0.530
YIPF5	ADRB2	psi-mi:“MI:0915”(physical association)	0.370
YIP5	YIPF5	psi-mi:“MI:0915”(physical association)	0.370
Cdc16	ANAPC15	psi-mi:“MI:0914”(association)	0.350
Cep131	WBP2	psi-mi:“MI:0914”(association)	0.350
Tnpo1	CCHCR1	psi-mi:“MI:0914”(association)	0.350
Pcgf1	SCAMP3	psi-mi:“MI:0914”(association)	0.350
Atp7a	RTL8C	psi-mi:“MI:0914”(association)	0.350
Ercc6l	RPL17	psi-mi:“MI:0914”(association)	0.350
RAB5C	GCA	psi-mi:“MI:0914”(association)	0.350
Psmb5		psi-mi:“MI:0914”(association)	0.350
RAB7A		psi-mi:“MI:0914”(association)	0.350
Atp2a2	ESYT2	psi-mi:“MI:0914”(association)	0.350
Pfdn2	SF1	psi-mi:“MI:0914”(association)	0.350
Hsf1	OFD1	psi-mi:“MI:0914”(association)	0.350
Uso1	SLC30A6	psi-mi:“MI:0914”(association)	0.350
VAPA		psi-mi:“MI:0914”(association)	0.350
MBOAT1	DERL1	psi-mi:“MI:0914”(association)	0.350
YIPF5	SSR3	psi-mi:“MI:0914”(association)	0.350

BioGRID (174): ATP1A1 (Affinity Capture-MS), ATP5A1 (Affinity Capture-MS), ATP5B (Affinity Capture-MS), ATP5O (Affinity Capture-MS), CAV1 (Affinity Capture-MS), COX5B (Affinity Capture-MS), COX6B1 (Affinity Capture-MS), PHB (Affinity Capture-MS), SLC1A5 (Affinity Capture-MS), SSR3 (Affinity Capture-MS), STX3 (Affinity Capture-MS), TAF9 (Affinity Capture-MS), CEPT1 (Affinity Capture-MS), YIF1A (Affinity Capture-MS), PHB2 (Affinity Capture-MS)

ESM2 similar proteins: A0A078H868, A4R0J5, A5D7K7, A6QLC6, B2WDD8, B8JLV7, B9RK42, O64614, O75694, O94348, P37199, Q0IJ20, Q28CH8, Q3B8G4, Q3UDR8, Q4FZQ0, Q4QQU5, Q4R5M4, Q54QY3, Q5BJH7, Q5E9E8, Q5F384, Q5R6W5, Q5U3G6, Q5XID0, Q66KA5, Q6GN58, Q6IQ85, Q6P301, Q6P5I8, Q6PC24, Q6TUD4, Q6ZQE4, Q7SXS2, Q7ZYA0, Q803Z2, Q8BR70, Q8N8F6, Q93VH1, Q93Z32

Diamond homologs: A5D7K7, O94348, P53039, Q4R5M4, Q54QY3, Q5E9E8, Q5R6W5, Q5XID0, Q5ZJD7, Q66KA5, Q6P5I8, Q7SXS2, Q8N8F6, Q969M3, Q9BSR8, Q9EQQ2, Q9JIM5, Q28CH8, Q54RZ2, Q5M7T4, Q8C407, A6QLC6, Q4QQU5, Q6NYF1, Q8BR70

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 105 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
cholesterol transport	5	42.1×	8e-05

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	2
Likely pathogenic	0
Uncertain significance	28
Likely benign	1
Benign	2

Top pathogenic / likely-pathogenic (2)

Variant ID	HGVS	Classification
1064542	NM_030799.9(YIPF5):c.542C>T (p.Ala181Val)	Pathogenic
1064545	NM_030799.9(YIPF5):c.652T>A (p.Trp218Arg)	Pathogenic

SpliceAI

603 predictions. Top by Δscore:

Variant	Effect	Δscore
5:144164253:AACT:A	acceptor_gain	1.0000
5:144164255:CT:C	acceptor_gain	1.0000
5:144164257:C:CC	acceptor_gain	1.0000
5:144165429:TA:T	donor_loss	1.0000
5:144165429:TAC:T	donor_gain	1.0000
5:144165430:A:AC	donor_gain	1.0000
5:144165430:A:C	donor_loss	1.0000
5:144165430:AC:A	donor_gain	1.0000
5:144165430:ACCTT:A	donor_gain	1.0000
5:144165431:C:CC	donor_gain	1.0000
5:144165431:C:CG	donor_loss	1.0000
5:144165431:CC:C	donor_gain	1.0000
5:144165431:CCTT:C	donor_gain	1.0000
5:144165431:CCTTC:C	donor_gain	1.0000
5:144165601:CTGT:C	acceptor_gain	1.0000
5:144165602:TGT:T	acceptor_gain	1.0000
5:144165603:GT:G	acceptor_gain	1.0000
5:144165605:C:CC	acceptor_gain	1.0000
5:144165607:A:C	acceptor_gain	1.0000
5:144165611:A:AC	acceptor_gain	1.0000
5:144165611:A:C	acceptor_gain	1.0000
5:144169844:A:AC	donor_gain	1.0000
5:144169845:C:CC	donor_gain	1.0000
5:144169866:T:TA	donor_gain	1.0000
5:144160555:TTCCT:T	acceptor_gain	0.9900
5:144160558:CT:C	acceptor_gain	0.9900
5:144160559:TC:T	acceptor_loss	0.9900
5:144160560:C:CC	acceptor_gain	0.9900
5:144160560:CT:C	acceptor_loss	0.9900
5:144162343:T:TA	donor_gain	0.9900

AlphaMissense

1673 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
5:144160443:G:T	P243H	1.000
5:144160503:G:T	A223D	1.000
5:144160511:A:C	S220R	1.000
5:144160511:A:T	S220R	1.000
5:144160513:T:G	S220R	1.000
5:144160519:A:G	W218R	1.000
5:144160519:A:T	W218R	1.000
5:144162260:G:C	P190R	1.000
5:144162260:G:T	P190H	1.000
5:144162268:A:C	C187W	1.000
5:144162273:A:G	Y186H	1.000
5:144162275:C:T	G185E	1.000
5:144162276:C:G	G185R	1.000
5:144162276:C:T	G185R	1.000
5:144162283:A:C	S182R	1.000
5:144162283:A:T	S182R	1.000
5:144162285:T:G	S182R	1.000
5:144162361:A:C	S156R	1.000
5:144162361:A:T	S156R	1.000
5:144162363:T:G	S156R	1.000
5:144164127:C:T	G138E	1.000
5:144164154:C:T	G129D	1.000
5:144164155:C:G	G129R	1.000
5:144164163:T:A	D126V	1.000
5:144164163:T:C	D126G	1.000
5:144160400:A:C	F257L	0.999
5:144160400:A:T	F257L	0.999
5:144160402:A:G	F257L	0.999
5:144160413:A:G	L253P	0.999
5:144160416:G:T	A252D	0.999

dbSNP variants (sampled 300 via entrez): RS1000244411 (5:144172261 G>A,T), RS1000489183 (5:144169551 C>T), RS1000490017 (5:144165986 G>A), RS1000501102 (5:144159311 T>C,G), RS1000553616 (5:144159503 G>T), RS1000562314 (5:144162560 G>T), RS1000841053 (5:144165752 T>C), RS1001139456 (5:144157944 G>A), RS1001404078 (5:144157663 CTT>C), RS1001727062 (5:144170956 A>G), RS1001781018 (5:144171540 T>A,C), RS1002343305 (5:144165281 T>C,G), RS1002589537 (5:144171052 C>T), RS1002782573 (5:144170239 C>T), RS1002794197 (5:144170458 C>A)

Disease associations

OMIM: gene MIM:611483 | disease phenotypes: MIM:619278

GenCC curated gene-disease

Disease	Classification	Inheritance
microcephaly, epilepsy, and diabetes syndrome 2	Strong	Autosomal recessive
primary microcephaly-epilepsy-permanent neonatal diabetes syndrome	Supportive	Autosomal recessive

Mondo (2): microcephaly, epilepsy, and diabetes syndrome 2 (MONDO:0025690), (MONDO:0013647)

Orphanet (0):

HPO phenotypes

9 total (9 of 9 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000252	Microcephaly
HP:0000819	Diabetes mellitus
HP:0001263	Global developmental delay
HP:0001518	Small for gestational age
HP:0002069	Bilateral tonic-clonic seizure
HP:0003593	Infantile onset
HP:0006956	Lateral ventricle dilatation
HP:0040217	Elevated hemoglobin A1c

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST009173_1	Response to (pegylated) interferon in HBeAG-positive hepatitis B	3.000000e-06
GCST010002_40	Refractive error	2.000000e-13

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0007859	response to interferon

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6067404 (SINGLE PROTEIN)

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

ChEMBL bioactivities

4 potent at pChembl≥5 of 4 total, top 4 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.23	Kd	59.48	nM	CHEMBL5653589
7.23	ED50	59.48	nM	CHEMBL5653589
5.71	Kd	1937	nM	CHEMBL3752910
5.71	ED50	1937	nM	CHEMBL3752910

PubChem BioAssay actives

2 with measured affinity, of 4 total; 2 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149797: Binding affinity to human YIPF5 incubated for 45 mins by Kinobead based pull down assay	kd	0.0595	uM
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149797: Binding affinity to human YIPF5 incubated for 45 mins by Kinobead based pull down assay	kd	1.9370	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Air Pollutants	affects expression, increases abundance, decreases expression	2
Valproic Acid	decreases expression, increases expression, affects expression	2
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression, increases expression	2
bisphenol F	increases expression	1
ginger extract	increases abundance, increases expression, decreases reaction	1
dicrotophos	decreases expression	1
methylmercuric chloride	decreases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	increases expression, decreases reaction, increases abundance	1
lead acetate	increases expression	1
sodium arsenite	increases expression	1
zinc chromate	increases abundance, increases expression	1
di-n-butylphosphoric acid	affects expression	1
chromium hexavalent ion	increases abundance, increases expression	1
CGP 52608	affects binding, increases reaction	1
K 7174	increases expression	1
ICG 001	increases expression	1
14-deoxy-11,12-didehydroandrographolide	increases expression	1
abrine	increases expression	1
bisphenol S	increases expression	1
NSC668394	increases expression	1
Resveratrol	affects cotreatment, increases expression	1
Cadmium	affects expression	1
Doxorubicin	increases expression	1
Ethyl Methanesulfonate	increases expression	1
Formaldehyde	increases expression	1
Ivermectin	decreases expression	1
Methyl Methanesulfonate	increases expression	1
Oils, Volatile	increases abundance, increases expression, decreases reaction	1
Ozone	increases abundance, affects expression	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5652839	Binding	Binding affinity to human YIPF5 incubated for 45 mins by Kinobead based pull down assay	NVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family. — ChemMedChem

Clinical trials (associated diseases)

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