POC1A

Summary

POC1A (POC1 centriolar protein A, HGNC:24488) is a protein-coding gene on chromosome 3p21.2, encoding POC1 centriolar protein homolog A (Q8NBT0). Plays an important role in centriole assembly and/or stability and ciliogenesis. It is a selective cancer dependency (DepMap: 18.8% of cell lines).

POC1 proteins contain an N-terminal WD40 domain and a C-terminal coiled coil domain and are part of centrosomes. They play an important role in basal body and cilia formation. This gene encodes one of the two POC1 proteins found in humans. Mutations in this gene result in short stature, onychodysplasia, facial dysmorphism, and hypotrichosis (SOFT) syndrome.

Source: NCBI Gene 25886 — RefSeq curated summary.

At a glance

• Gene–disease (curated): short stature-onychodysplasia-facial dysmorphism-hypotrichosis syndrome (Strong, GenCC)
• GWAS associations: 5
• Clinical variants (ClinVar): 243 total — 16 pathogenic, 10 likely-pathogenic
• Phenotypes (HPO): 48
• Cancer dependency (DepMap): dependent in 18.8% of screened cell lines
• MANE Select transcript: NM_015426

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:24488
Approved symbol	POC1A
Name	POC1 centriolar protein A
Location	3p21.2
Locus type	gene with protein product
Status	Approved
Aliases	DKFZP434C245
Ensembl gene	ENSG00000164087
Ensembl biotype	protein_coding
OMIM	614783
Entrez	25886

Gene structure

Transcript identifiers

Ensembl transcripts: 20 — 20 protein_coding

ENST00000296484, ENST00000394970, ENST00000474012, ENST00000939749, ENST00000939750, ENST00000939751, ENST00000939752, ENST00000939753, ENST00000939754, ENST00000939755, ENST00000939756, ENST00000939757, ENST00000939758, ENST00000939759, ENST00000939760, ENST00000939761, ENST00000939762, ENST00000939763, ENST00000939764, ENST00000939765

RefSeq mRNA: 3 — MANE Select: NM_015426 NM_001161580, NM_001161581, NM_015426

CCDS: CCDS2846, CCDS54591, CCDS54592

Canonical transcript exons

ENST00000296484 — 11 exons

Exon	Start	End
ENSE00001081285	52096569	52096712
ENSE00001081287	52125113	52125181
ENSE00001081288	52138169	52138302
ENSE00001081289	52145846	52145961
ENSE00001081290	52149210	52149389
ENSE00001081291	52146988	52147095
ENSE00001081292	52122379	52122477
ENSE00001124947	52151016	52151100
ENSE00001243451	52075226	52075985
ENSE00001833005	52154355	52154423
ENSE00003508643	52149816	52149987

Expression profiles

Bgee: expression breadth ubiquitous, 164 present calls, max score 87.62.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 6.1553 / max 44.3196, expressed in 1316 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
42406	6.1553	1316

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
pancreatic ductal cell	CL:0002079	87.62	silver quality
ventricular zone	UBERON:0003053	85.56	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	84.36	gold quality
ileal mucosa	UBERON:0000331	84.28	silver quality
left testis	UBERON:0004533	83.12	gold quality
right testis	UBERON:0004534	83.10	gold quality
ganglionic eminence	UBERON:0004023	82.13	gold quality
mucosa of transverse colon	UBERON:0004991	81.99	gold quality
testis	UBERON:0000473	80.92	gold quality
sperm	CL:0000019	80.34	silver quality
stromal cell of endometrium	CL:0002255	76.56	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	75.76	gold quality
rectum	UBERON:0001052	75.31	gold quality
endothelial cell	CL:0000115	75.16	silver quality
right adrenal gland	UBERON:0001233	74.80	gold quality
right adrenal gland cortex	UBERON:0035827	73.95	gold quality
left adrenal gland	UBERON:0001234	73.30	gold quality
left adrenal gland cortex	UBERON:0035825	72.14	gold quality
right lobe of liver	UBERON:0001114	72.13	gold quality
vermiform appendix	UBERON:0001154	72.13	gold quality
esophagus mucosa	UBERON:0002469	72.04	gold quality
lower esophagus mucosa	UBERON:0035834	71.37	gold quality
adrenal gland	UBERON:0002369	70.61	gold quality
smooth muscle tissue	UBERON:0001135	70.49	gold quality
adrenal cortex	UBERON:0001235	70.27	gold quality
bone marrow cell	CL:0002092	70.12	silver quality
prefrontal cortex	UBERON:0000451	69.61	gold quality
granulocyte	CL:0000094	69.58	gold quality
transverse colon	UBERON:0001157	69.21	gold quality
lymph node	UBERON:0000029	68.28	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ENAD-17	yes	197.90
E-ANND-3	no	3.45

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

11 targeting POC1A, 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-3925-3P	100.00	69.95	1237
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-10527-5P	99.91	72.28	3754
HSA-MIR-4503	99.85	71.45	1869
HSA-MIR-1976	99.74	65.48	1127
HSA-MIR-1303	99.65	69.77	1662
HSA-MIR-4764-5P	98.88	65.53	894
HSA-MIR-2467-3P	98.65	67.18	1969
HSA-MIR-6773-5P	97.04	64.30	595
HSA-MIR-6724-5P	96.41	63.11	507
HSA-MIR-3918	96.13	64.65	1300

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 18.8% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 11)

• Based on these data, we propose that Pix1 and Pix2 are microtubule-associated adaptor proteins that likely contribute to a range of developmental and cell division processes. (PMID:18068700)
• Short stature, onychodysplasia, facial dysmorphism, and hypotrichosis syndrome is caused by a POC1A mutation. (PMID:22840363)
• POC1A truncation mutation causes a ciliopathy in humans characterized by primordial dwarfism. (PMID:22840364)
• Poc1A and Poc1B play redundant, but essential, roles in generation of stable centrioles, but Poc1B may have additional independent functions during cell cycle progression. (PMID:23015594)
• Result identified a novel mutation in POC1A of patients with primordial dwarfism and showed that this mutation causes the formation of multiple numbers of centrioles and multipolar spindles with abnormal chromosome arrangement. (PMID:26162852)
• POC1A may be added to ALMS1 and PCNT as examples of centrosomal or pericentriolar proteins whose dysfunction leads to extreme dyslipidaemic insulin resistance. (PMID:26336158)
• we report the first patient with SOFT syndrome harboring compound heterozygous variants of POC1A. understanding POC1A mutations may provide appropriate management and genetic counseling to these patients and their families. (PMID:26791357)
• Biallelic POC1A variants cause syndromic severe insulin resistance with muscle cramps. (PMID:35234134)
• POC1A, prognostic biomarker of immunosuppressive microenvironment in cancer. (PMID:35748773)
• Ciliopathy due to POC1A deficiency: clinical and metabolic features, and cellular modeling. (PMID:38245004)
• Upregulation of POC1A in lung adenocarcinoma promotes tumour progression and predicts poor prognosis. (PMID:38429900)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	poc1a	ENSDARG00000078533
mus_musculus	Poc1a	ENSMUSG00000023345
rattus_norvegicus	Poc1a	ENSRNOG00000037295

Paralogs (26): PAFAH1B1 (ENSG00000007168), SNRNP40 (ENSG00000060688), WDR62 (ENSG00000075702), WDR7 (ENSG00000091157), TBL2 (ENSG00000106638), PAK1IP1 (ENSG00000111845), WDR75 (ENSG00000115368), DCAF4 (ENSG00000119599), DAW1 (ENSG00000123977), TEP1 (ENSG00000129566), AHI1 (ENSG00000135541), WDR38 (ENSG00000136918), MAPKBP1 (ENSG00000137802), POC1B (ENSG00000139323), NEDD1 (ENSG00000139350), COP1 (ENSG00000143207), WDR17 (ENSG00000150627), WDR43 (ENSG00000163811), WDR88 (ENSG00000166359), WDR81 (ENSG00000167716), DCAF4L2 (ENSG00000176566), DCAF4L1 (ENSG00000182308), WDR27 (ENSG00000184465), NWD1 (ENSG00000188039), WDR5 (ENSG00000196363), WDR5B (ENSG00000196981)

Protein

Protein identifiers

POC1 centriolar protein homolog A — Q8NBT0 (reviewed: Q8NBT0)

Alternative names: Pix2, Proteome of centriole protein 1A, WD repeat-containing protein 51A

All UniProt accessions (1): Q8NBT0

UniProt curated annotations — full annotation on UniProt →

Function. Plays an important role in centriole assembly and/or stability and ciliogenesis. Involved in early steps of centriole duplication, as well as in the later steps of centriole length control. Acts in concert with POC1B to ensure centriole integrity and proper mitotic spindle formation.

Subunit / interactions. Interacts with POC1B.

Subcellular location. Cytoplasm. Cytoskeleton. Microtubule organizing center. Centrosome. Centriole. Cilium basal body. Spindle pole.

Disease relevance. Short stature, onychodysplasia, facial dysmorphism, and hypotrichosis (SOFT) [MIM:614813] A syndrome characterized by severely short long bones, peculiar facies associated with paucity of hair, and nail anomalies. Growth retardation is evident on prenatal ultrasound as early as the second trimester of pregnancy, and affected individuals reach a final stature consistent with a height age of 6 years to 8 years. Relative macrocephaly is present during early childhood but head circumference is markedly low by adulthood. Psychomotor development is normal. Facial dysmorphism includes a long, triangular face with prominent nose and small ears, and affected individuals have an unusual high-pitched voice. Clinodactyly, brachydactyly, and hypoplastic distal phalanges and fingernails are present in association with postpubertal sparse and short hair. Typical skeletal findings include short and thick long bones with mild irregular metaphyseal changes, short femoral necks, and hypoplastic pelvis and sacrum. All long bones of the hand are short, with major delay of carpal ossification and cone-shaped epiphyses. Vertebral body ossification is also delayed. The disease is caused by variants affecting the gene represented in this entry. Cells derived from affected individuals have abnormal mitotic mechanics with multipolar spindles, in addition to clearly impaired ciliogenesis.

Similarity. Belongs to the WD repeat POC1 family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q8NBT0-1	1	yes
Q8NBT0-2	2
Q8NBT0-3	3

RefSeq proteins (3): NP_001155052, NP_001155053, NP_056241* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001680	WD40_rpt	Repeat
IPR015943	WD40/YVTN_repeat-like_dom_sf	Homologous_superfamily
IPR019775	WD40_repeat_CS	Conserved_site
IPR020472	WD40_PAC1	Repeat
IPR036322	WD40_repeat_dom_sf	Homologous_superfamily
IPR050505	WDR55/POC1	Family

Pfam: PF00400

UniProt features (15 total): repeat 7, sequence variant 3, splice variant 2, chain 1, sequence conflict 1, coiled-coil region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8NBT0-F1	85.17	0.66

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 280 (showing top): GOBP_REGULATION_OF_MICROTUBULE_BASED_PROCESS, GOBP_CARTILAGE_DEVELOPMENT, GOBP_SKELETAL_SYSTEM_DEVELOPMENT, GOBP_GROWTH, AACYNNNNTTCCS_UNKNOWN, GOBP_MALE_GAMETE_GENERATION, GOBP_CHONDROCYTE_DEVELOPMENT, GOBP_BONE_GROWTH, GOCC_MICROTUBULE_ORGANIZING_CENTER, GOBP_ANIMAL_ORGAN_MORPHOGENESIS, GOBP_BONE_DEVELOPMENT, GOBP_CILIUM_ORGANIZATION, GOBP_CHONDROCYTE_DIFFERENTIATION, GOBP_REGULATION_OF_CELL_CYCLE, GOCC_CENTROSOME

GO Biological Process (8): growth plate cartilage chondrocyte development (GO:0003431), mitotic spindle organization (GO:0007052), spermatogenesis (GO:0007283), positive regulation of centrosome duplication (GO:0010825), cilium assembly (GO:0060271), non-motile cilium assembly (GO:1905515), cell projection organization (GO:0030030), bone development (GO:0060348)

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

GO Cellular Component (7): spindle pole (GO:0000922), cytoplasm (GO:0005737), centrosome (GO:0005813), centriole (GO:0005814), ciliary basal body (GO:0036064), cytoskeleton (GO:0005856), cell projection (GO:0042995)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
microtubule organizing center	3
intracellular membraneless organelle	2
growth plate cartilage chondrocyte differentiation	1
chondrocyte development involved in endochondral bone morphogenesis	1
mitotic cell cycle	1
spindle organization	1
microtubule cytoskeleton organization involved in mitosis	1
developmental process involved in reproduction	1
male gamete generation	1
regulation of centrosome duplication	1
centrosome duplication	1
positive regulation of cell cycle process	1
axoneme assembly	1
intraciliary transport involved in cilium assembly	1
cilium organization	1
protein localization to cilium	1
organelle assembly	1
trans-Golgi to periciliary membrane compartment transport	1
plasma membrane bounded cell projection assembly	1
ciliary transition zone assembly	1
cilium assembly	1
cellular component organization	1
skeletal system development	1
animal organ development	1
binding	1
spindle	1
intracellular anatomical structure	1
centriole	1
cilium	1

Protein interactions and networks

STRING

2314 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
POC1A	CENPW	Q5EE01	617
POC1A	PLK4	O00444	547
POC1A	CEP135	Q66GS9	543
POC1A	CEP295	Q9C0D2	526
POC1A	SASS6	Q6UVJ0	516
POC1A	CPAP	Q9HC77	515
POC1A	IQCF6	A8MYZ5	494
POC1A	PCNT	O95613	487
POC1A	NPHP4	O75161	461
POC1A	CEP120	Q8N960	461
POC1A	NPHP1	O15259	455
POC1A	SPICE1	Q8N0Z3	447
POC1A	CEP19	Q96LK0	446
POC1A	POC5	Q8NA72	443
POC1A	NSMCE2	Q96MF7	436

IntAct

100 interactions, top by confidence:

A	B	Type	Score
SIL1	HSPA5	psi-mi:“MI:0914”(association)	0.740
BRK1	HSBP1	psi-mi:“MI:0914”(association)	0.740
NUDC	POC1A	psi-mi:“MI:0915”(physical association)	0.730
IFT57	IFT56	psi-mi:“MI:0914”(association)	0.640
AKIP1	POC1A	psi-mi:“MI:0914”(association)	0.610
MDM1	POC1A	psi-mi:“MI:0915”(physical association)	0.590
CALR	POC1A	psi-mi:“MI:0915”(physical association)	0.560
POC1A	CDH1	psi-mi:“MI:0915”(physical association)	0.560
DLST	POC1A	psi-mi:“MI:0915”(physical association)	0.560
POC1A	PECAM1	psi-mi:“MI:0915”(physical association)	0.560
POC1A	NEK7	psi-mi:“MI:0915”(physical association)	0.560
HTT	POC1A	psi-mi:“MI:0915”(physical association)	0.560
ATXN3	POC1A	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (174): CCT7 (Affinity Capture-MS), CCT4 (Affinity Capture-MS), HSPA8 (Affinity Capture-MS), HSPA6 (Affinity Capture-MS), HSPA1L (Affinity Capture-MS), CCT6A (Affinity Capture-MS), CCT8 (Affinity Capture-MS), CCT3 (Affinity Capture-MS), TCP1 (Affinity Capture-MS), POC1B (Affinity Capture-MS), CCT5 (Affinity Capture-MS), CCT2 (Affinity Capture-MS), PDCL (Affinity Capture-MS), TXNDC9 (Affinity Capture-MS), CORO1A (Affinity Capture-MS)

ESM2 similar proteins: A0JP70, A2CEH0, B0X2V9, B3MET8, B3NSK1, B4GIJ0, B4HND9, B4J8H6, B4KRQ4, B4MFM2, B4P7H8, B4QB64, D3ZW91, F6ZT52, O00423, O61585, Q05B17, Q05BC3, Q16MY0, Q1LZ08, Q28I85, Q28YY2, Q2TBP4, Q32PG3, Q4R2Z6, Q4V7Y7, Q4V7Z1, Q4V8C3, Q5F3K4, Q5RAW8, Q5RD06, Q5ZIU8, Q5ZLG9, Q6NVM2, Q6PFM9, Q6PJI9, Q6S7B0, Q7T0P4, Q7ZUV2, Q7ZVF0

Diamond homologs: A2CEH0, D3ZW91, F6ZT52, Q229Z6, Q28I85, Q2TBP4, Q4V7Z1, Q5RD06, Q6NWV3, Q6NYH1, Q7T0P4, Q7ZVF0, Q8BHD1, Q8JZX3, Q8NBT0, Q8TC44, Q9VU65, B6QC06, Q9FLX9, Q9HBG6

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	16
Likely pathogenic	10
Uncertain significance	88
Likely benign	93
Benign	15

Top pathogenic / likely-pathogenic (26)

Variant ID	HGVS	Classification
1192285	NM_015426.5(POC1A):c.981+1G>A	Pathogenic
1323481	NM_015426.5(POC1A):c.667_668dup (p.Gln223fs)	Pathogenic
1458947	NC_000003.11:g.(?52172193)(52212093_?)del	Pathogenic
2426147	NC_000003.11:g.(?52188351)(52188388_?)del	Pathogenic
2428762	NM_015426.5(POC1A):c.80_81insA (p.Phe27fs)	Pathogenic
2957391	NM_015426.5(POC1A):c.2T>C (p.Met1Thr)	Pathogenic
3256658	NM_015426.5(POC1A):c.689_696del (p.Ala230fs)	Pathogenic
37062	NM_015426.5(POC1A):c.241C>T (p.Arg81Ter)	Pathogenic
37063	NM_015426.5(POC1A):c.512T>C (p.Leu171Pro)	Pathogenic
3899919	NM_015426.5(POC1A):c.719C>T (p.Ser240Leu)	Pathogenic
4085991	NM_015426.5(POC1A):c.53del (p.His18fs)	Pathogenic
504327	NM_015426.5(POC1A):c.707_708del (p.Ser236fs)	Pathogenic
981225	NM_015426.5(POC1A):c.884del (p.Val295fs)	Pathogenic
981226	NM_015426.5(POC1A):c.1048del (p.Gln350fs)	Pathogenic
996335	NM_015426.5(POC1A):c.850dup (p.Glu284fs)	Pathogenic
996336	NM_015426.5(POC1A):c.593_605del (p.Ser198fs)	Pathogenic
1690956	NM_015426.5(POC1A):c.893G>A (p.Trp298Ter)	Likely pathogenic
1945579	NM_015426.5(POC1A):c.882+1G>A	Likely pathogenic
1946319	NM_015426.5(POC1A):c.276-2A>T	Likely pathogenic
2108325	NM_015426.5(POC1A):c.814-4_814-2del	Likely pathogenic
3250429	NM_015426.5(POC1A):c.55C>T (p.Arg19Ter)	Likely pathogenic
3341413	NM_015426.5(POC1A):c.104-2A>C	Likely pathogenic
3589458	NM_015426.5(POC1A):c.483_484del (p.Ser162fs)	Likely pathogenic
3589459	NM_015426.5(POC1A):c.104-2del	Likely pathogenic
431918	NM_015426.5(POC1A):c.370G>A (p.Asp124Asn)	Likely pathogenic
623370	NM_015426.5(POC1A):c.64G>T (p.Val22Phe)	Likely pathogenic

SpliceAI

2815 predictions. Top by Δscore:

Variant	Effect	Δscore
3:52075982:CTGT:C	acceptor_gain	1.0000
3:52075983:TGT:T	acceptor_gain	1.0000
3:52075984:GTCT:G	acceptor_loss	1.0000
3:52075986:C:CC	acceptor_gain	1.0000
3:52122372:CACTT:C	donor_loss	1.0000
3:52122373:ACTTA:A	donor_loss	1.0000
3:52122374:CTTAC:C	donor_loss	1.0000
3:52122375:TTA:T	donor_loss	1.0000
3:52122376:TA:T	donor_loss	1.0000
3:52122377:A:AG	donor_loss	1.0000
3:52124220:T:A	donor_gain	1.0000
3:52125107:ACTT:A	donor_loss	1.0000
3:52125109:TTAC:T	donor_loss	1.0000
3:52125111:A:AC	donor_gain	1.0000
3:52125111:ACT:A	donor_loss	1.0000
3:52125112:C:CC	donor_gain	1.0000
3:52125112:C:T	donor_loss	1.0000
3:52125112:CTT:C	donor_gain	1.0000
3:52125112:CTTG:C	donor_gain	1.0000
3:52125180:CC:C	acceptor_gain	1.0000
3:52125181:CC:C	acceptor_gain	1.0000
3:52125182:C:CC	acceptor_gain	1.0000
3:52125182:CTGG:C	acceptor_loss	1.0000
3:52125183:T:C	acceptor_loss	1.0000
3:52125186:C:CT	acceptor_gain	1.0000
3:52125187:A:T	acceptor_gain	1.0000
3:52145844:A:AC	donor_gain	1.0000
3:52145845:C:CC	donor_gain	1.0000
3:52145845:CA:C	donor_gain	1.0000
3:52145957:CAAAG:C	acceptor_gain	1.0000

AlphaMissense

2673 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:52147037:A:G	W172R	1.000
3:52147037:A:T	W172R	1.000
3:52147055:C:G	D166H	1.000
3:52147059:A:C	S164R	1.000
3:52147059:A:T	S164R	1.000
3:52147060:C:A	S164I	1.000
3:52147061:T:G	S164R	1.000
3:52149294:T:A	D124V	1.000
3:52149295:C:G	D124H	1.000
3:52149306:G:T	T120K	1.000
3:52149829:A:G	W88R	1.000
3:52149829:A:T	W88R	1.000
3:52149983:A:C	S36R	1.000
3:52149983:A:T	S36R	1.000
3:52149985:T:G	S36R	1.000
3:52122468:A:G	W298R	0.999
3:52122468:A:T	W298R	0.999
3:52125133:A:G	S288P	0.999
3:52125135:G:T	A287D	0.999
3:52138245:G:T	T246K	0.999
3:52138251:A:G	L244P	0.999
3:52145917:G:T	A203D	0.999
3:52147035:C:A	W172C	0.999
3:52147035:C:G	W172C	0.999
3:52147045:A:T	V169D	0.999
3:52147054:T:A	D166V	0.999
3:52147054:T:G	D166A	0.999
3:52147066:G:A	S162F	0.999
3:52147066:G:T	S162Y	0.999
3:52147067:A:G	S162P	0.999

dbSNP variants (sampled 300 via entrez): RS1000076023 (3:52150301 A>C), RS1000109071 (3:52106656 T>C), RS1000202035 (3:52125611 A>C), RS1000205049 (3:52110398 G>A), RS1000232147 (3:52130298 C>A,T), RS1000277964 (3:52093576 T>A,C), RS1000306812 (3:52154548 G>A,C), RS1000321467 (3:52080825 A>G), RS1000328109 (3:52131823 G>C), RS1000356319 (3:52144426 G>A,C), RS1000450655 (3:52104338 T>C,G), RS1000499069 (3:52116516 C>T), RS1000507836 (3:52097093 T>C), RS1000520207 (3:52082316 C>T), RS1000525598 (3:52126962 A>G)

Disease associations

OMIM: gene MIM:614783 | disease phenotypes: MIM:614813, MIM:262400

GenCC curated gene-disease

Disease	Classification	Inheritance
short stature-onychodysplasia-facial dysmorphism-hypotrichosis syndrome	Strong	Autosomal recessive

Mondo (3): short stature-onychodysplasia-facial dysmorphism-hypotrichosis syndrome (MONDO:0013894), isolated growth hormone deficiency type IA (MONDO:0009876), microcephaly (MONDO:0001149)

Orphanet (3): Short stature-onychodysplasia-facial dysmorphism-hypotrichosis syndrome (Orphanet:314394), Isolated growth hormone deficiency type IA (Orphanet:231662), Non-acquired isolated growth hormone deficiency (Orphanet:631)

HPO phenotypes

48 total (30 of 48 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000060	Clitoral hypoplasia
HP:0000164	Abnormality of the dentition
HP:0000252	Microcephaly
HP:0000256	Macrocephaly
HP:0000276	Long face
HP:0000303	Mandibular prognathia
HP:0000307	Pointed chin
HP:0000316	Hypertelorism
HP:0000325	Triangular face
HP:0000343	Long philtrum
HP:0000348	High forehead
HP:0000358	Posteriorly rotated ears
HP:0000369	Low-set ears
HP:0000448	Prominent nose
HP:0000455	Broad nasal tip
HP:0000490	Deeply set eye
HP:0000798	Oligozoospermia
HP:0000819	Diabetes mellitus
HP:0000938	Osteopenia
HP:0001156	Brachydactyly
HP:0001252	Hypotonia
HP:0001263	Global developmental delay
HP:0001290	Generalized hypotonia
HP:0001508	Failure to thrive
HP:0001510	Growth delay
HP:0001518	Small for gestational age
HP:0001620	Abnormally high-pitched voice
HP:0001773	Short foot
HP:0001792	Small nail

GWAS associations

5 associations (top):

Study	Trait	p-value
GCST012353_28	Serum metabolite concentrations in chronic kidney disease	5.000000e-13
GCST012353_29	Serum metabolite concentrations in chronic kidney disease	6.000000e-13
GCST012353_30	Serum metabolite concentrations in chronic kidney disease	2.000000e-12
GCST90020024_1199	A body shape index	2.000000e-08
GCST90020029_1186	Waist circumference adjusted for body mass index	1.000000e-11

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0007789	BMI-adjusted waist circumference

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D008831	Microcephaly	C05.660.207.620; C10.500.507.400.500; C16.131.621.207.620; C16.131.666.507.400.500
C537404	Pituitary dwarfism 1 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	increases abundance, increases expression, affects cotreatment, decreases expression	5
Arsenic	increases abundance, increases expression, affects cotreatment, decreases expression	2
Benzo(a)pyrene	affects methylation, decreases expression	2
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	2
propionaldehyde	decreases expression	1
bisphenol A	decreases expression	1
quercitrin	decreases expression	1
arsenite	affects binding, increases reaction	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
perfluorooctanoic acid	decreases expression	1
zinc chromate	decreases expression, increases abundance	1
manganese chloride	affects cotreatment, decreases expression, increases abundance	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
aflatoxin B2	increases methylation	1
isobutyl alcohol	increases abundance, affects cotreatment, decreases expression	1
diallyl trisulfide	decreases expression	1
epigallocatechin gallate	decreases expression, affects cotreatment	1
chromium hexavalent ion	decreases expression, increases abundance	1
2-palmitoylglycerol	increases expression	1
ICG 001	increases expression	1
abrine	decreases expression	1
jinfukang	increases expression	1
Sunitinib	decreases expression	1
Leflunomide	decreases expression	1
Acetaminophen	increases expression	1
Calcitriol	decreases expression, affects cotreatment	1
Cisplatin	increases expression	1
Coumestrol	increases expression	1
Dichlorodiphenyl Dichloroethylene	increases expression	1
Gasoline	affects cotreatment, decreases expression, increases abundance	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT05518188	PHASE1/PHASE2	RECRUITING	Melpida: Recombinant Adeno-associated Virus (serotype 9) Encoding a Codon Optimized Human AP4M1 Transgene (hAP4M1opt)
NCT00001639	Not specified	COMPLETED	Evaluation of Patients With Unresolved Chromosome Abnormalities
NCT01151462	Not specified	WITHDRAWN	Postnatal HCMV Infection in Very Preterm Infants. Implications, Morbidity, Growth and Neurodevelopmental Outcomes.
NCT01565005	Not specified	COMPLETED	Microcephaly Genetic Deficiency in Neural Progenitors
NCT02510170	Not specified	COMPLETED	Fetal and Maternal Head Circumference During Pregnancy in Israeli Population
NCT02741882	Not specified	COMPLETED	Zika and Microcephaly: Case-control Study
NCT02943304	Not specified	COMPLETED	Neurodevelopment Outcome of Newborns Exposed to Zika Virus (ZIKV) in Utero
NCT03255369	Not specified	UNKNOWN	Vertical Exposure to Zika Virus and Its Consequences for Child Neurodevelopment (ZIKVIRUSIFF)
NCT03325946	Not specified	RECRUITING	The FBRI VTC Neuromotor Research Clinic
NCT03330600	Not specified	COMPLETED	Efficacy of Aquatic Physiotherapy in Children With Microcephaly by Zika Virus Congenital Syndrome
NCT03548779	Not specified	COMPLETED	North Carolina Genomic Evaluation by Next-generation Exome Sequencing, 2
NCT03651687	Not specified	COMPLETED	Guangzhou Surveillance and Clinical Study in Microcephaly (GSCSM)
NCT03922594	Not specified	TERMINATED	Surveillance of Zika-related Microcephaly in Sub-Saharan Africa and Asia
NCT04816175	Not specified	COMPLETED	Intensive Therapy for Children With Microcephaly, Hyperkinetic Movements, or Global Developmental Delay
NCT05322980	Not specified	COMPLETED	Summary of Infants Weighing 500 Grams or Less
NCT06019182	Not specified	RECRUITING	MEHMO Natural History and Biomarkers
NCT06566066	Not specified	RECRUITING	Register for Patients With Thyroid Hormone Resistance.