DONSON

Summary

DONSON (DNA replication fork stabilization factor DONSON, HGNC:2993) is a protein-coding gene on chromosome 21q22.11, encoding Protein downstream neighbor of Son (Q9NYP3). Replisome component that maintains genome stability by protecting stalled or damaged replication forks. It is a common-essential gene (DepMap: required in 99.8% of cancer cell lines).

This gene lies downstream of the SON gene and spans 10 kb on chromosome 21. The function of this gene is unknown.

Source: NCBI Gene 29980 — RefSeq curated summary.

At a glance

• Gene–disease (curated): microcephaly, short stature, and limb abnormalities (Strong, GenCC) — +1 more curated relationship
• GWAS associations: 1
• Clinical variants (ClinVar): 311 total — 31 pathogenic, 12 likely-pathogenic
• Phenotypes (HPO): 46
• Cancer dependency (DepMap): dependent in 99.8% of screened cell lines (common-essential)
• MANE Select transcript: NM_017613

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:2993
Approved symbol	DONSON
Name	DNA replication fork stabilization factor DONSON
Location	21q22.11
Locus type	gene with protein product
Status	Approved
Aliases	B17, C2TA, DKFZP434M035
Ensembl gene	ENSG00000159147
Ensembl biotype	protein_coding
OMIM	611428
Entrez	29980

Gene structure

Transcript identifiers

Ensembl transcripts: 26 — 19 protein_coding, 5 nonsense_mediated_decay, 2 retained_intron

ENST00000303071, ENST00000303113, ENST00000417871, ENST00000432378, ENST00000437395, ENST00000439593, ENST00000440810, ENST00000442660, ENST00000444517, ENST00000453626, ENST00000457359, ENST00000460557, ENST00000462566, ENST00000858799, ENST00000858800, ENST00000858801, ENST00000858802, ENST00000858803, ENST00000936411, ENST00000936412, ENST00000936413, ENST00000936414, ENST00000936415, ENST00000966265, ENST00000966266, ENST00000966267

RefSeq mRNA: 1 — MANE Select: NM_017613 NM_017613

CCDS: CCDS13632

Canonical transcript exons

ENST00000303071 — 10 exons

Exon	Start	End
ENSE00001237873	33587522	33587602
ENSE00001363113	33577551	33578444
ENSE00001363177	33588321	33588684
ENSE00003539477	33585978	33586181
ENSE00003561968	33582165	33582246
ENSE00003563368	33584590	33584768
ENSE00003571961	33581951	33582055
ENSE00003588206	33583488	33583666
ENSE00003597599	33581302	33581500
ENSE00003660298	33579350	33579562

Expression profiles

Bgee: expression breadth ubiquitous, 247 present calls, max score 94.24.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 19.1013 / max 216.6662, expressed in 1779 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
190263	18.3513	1774
190262	0.7500	414

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
ventricular zone	UBERON:0003053	94.24	gold quality
right testis	UBERON:0004534	94.24	gold quality
left testis	UBERON:0004533	94.06	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	93.51	gold quality
ganglionic eminence	UBERON:0004023	93.43	gold quality
testis	UBERON:0000473	92.10	gold quality
left ovary	UBERON:0002119	91.35	gold quality
embryo	UBERON:0000922	90.93	gold quality
lower esophagus mucosa	UBERON:0035834	90.42	gold quality
right ovary	UBERON:0002118	90.40	gold quality
cerebellar hemisphere	UBERON:0002245	90.22	gold quality
tibial nerve	UBERON:0001323	90.12	gold quality
cerebellar cortex	UBERON:0002129	89.95	gold quality
cortical plate	UBERON:0005343	89.60	gold quality
right hemisphere of cerebellum	UBERON:0014890	89.50	gold quality
adenohypophysis	UBERON:0002196	89.48	gold quality
right lobe of liver	UBERON:0001114	89.00	gold quality
stromal cell of endometrium	CL:0002255	88.56	gold quality
endocervix	UBERON:0000458	88.45	gold quality
ovary	UBERON:0000992	88.30	gold quality
cerebellum	UBERON:0002037	87.92	gold quality
body of uterus	UBERON:0009853	87.82	gold quality
left uterine tube	UBERON:0001303	87.80	gold quality
right uterine tube	UBERON:0001302	87.56	gold quality
pituitary gland	UBERON:0000007	87.35	gold quality
mucosa of transverse colon	UBERON:0004991	87.34	gold quality
ectocervix	UBERON:0012249	87.34	gold quality
calcaneal tendon	UBERON:0003701	87.17	gold quality
skin of abdomen	UBERON:0001416	87.06	gold quality
skin of leg	UBERON:0001511	86.99	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-MTAB-8205	yes	1307.73
E-MTAB-8142	yes	15.45
E-ANND-3	yes	3.45

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): YY1

miRNA regulators (miRDB)

48 targeting DONSON, 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-8485	100.00	77.57	4731
HSA-MIR-4682	100.00	68.89	1258
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-4666A-3P	99.96	71.71	3434
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-4496	99.88	68.89	2236
HSA-MIR-30A-3P	99.87	69.74	2928
HSA-MIR-30D-3P	99.87	69.92	2917
HSA-MIR-30E-3P	99.87	69.68	2942
HSA-MIR-4503	99.85	71.45	1869
HSA-MIR-199A-3P	99.75	70.48	929
HSA-MIR-199B-3P	99.75	70.48	929
HSA-MIR-3129-5P	99.75	70.46	914
HSA-MIR-3059-5P	99.70	69.93	2491
HSA-MIR-12124	99.68	69.17	2700
HSA-MIR-26A-1-3P	99.64	66.81	788
HSA-MIR-26A-2-3P	99.64	66.82	786
HSA-MIR-6083	99.47	68.73	2393
HSA-MIR-145-3P	99.33	67.66	764
HSA-MIR-20B-3P	99.29	67.05	784
HSA-MIR-7158-5P	99.25	67.95	796
HSA-MIR-8065	99.19	70.38	1289
HSA-MIR-8066	99.05	68.66	1532
HSA-MIR-670-3P	99.03	68.88	2404

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 99.8% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 10)

• Aberrant splicing and a noncoding mutation in DONSON gene is the cause of microcephaly-micromelia syndrome (PMID:28630177)
• we present the clinical data of siblings with microcephaly, short stature, and limb abnormalities syndrome (MISSLA) featuring a novel DONSON variant and summarize the current literature on MISSLA. (PMID:31320746)
• four unrelated families with five affected individuals having biallelic or de novo variants in DONSON presenting with a core phenotype of severe short stature (z score < -3 SD), additional skeletal abnormalities, and microcephaly, were identified. (PMID:31407851)
• Linked-read genome sequencing identifies biallelic pathogenic variants in DONSON as a novel cause of Meier-Gorlin syndrome. (PMID:31784481)
• the antitumor miR-101-5p/DONSON axis and its modulated replisome genes might be a novel diagnostic and therapeutic target for clear cell renal cell carcinoma (PMID:31975570)
• Circ-DONSON promotes malignant progression of glioma through modulating FOXO3. (PMID:32016978)
• DONSON and FANCM associate with different replisomes distinguished by replication timing and chromatin domain. (PMID:32769987)
• Novel role of DONSON in CMG helicase assembly during vertebrate DNA replication initiation. (PMID:37458194)
• DONSON facilitates Cdc45 and GINS chromatin association and is essential for DNA replication initiation. (PMID:37638758)
• DONSON is required for CMG helicase assembly in the mammalian cell cycle. (PMID:37781960)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
mus_musculus	Donson	ENSMUSG00000022960
rattus_norvegicus	Donson	ENSRNOG00000002012
drosophila_melanogaster	hd	FBGN0086695
caenorhabditis_elegans		WBGENE00016074

Protein

Protein identifiers

Protein downstream neighbor of Son — Q9NYP3 (reviewed: Q9NYP3)

Alternative names: B17

All UniProt accessions (11): C9J4K5, C9JSP0, Q9NYP3, F8W8A5, F8WC22, F8WD19, H7C006, H7C1C1, H7C1M7, H7C304, V9GY84

UniProt curated annotations — full annotation on UniProt →

Function. Replisome component that maintains genome stability by protecting stalled or damaged replication forks. After the induction of replication stress, required for the stabilization of stalled replication forks, the efficient activation of the intra-S-phase and G/2M cell-cycle checkpoints and the maintenance of genome stability.

Subunit / interactions. Component of the replisome complex composed of at least DONSON, MCM2, MCM7, PCNA and TICRR; interaction at least with PCNA occurs during DNA replication.

Subcellular location. Nucleus.

Tissue specificity. Expressed in the brain, with higher levels in prenatal compared to adult brain.

Disease relevance. Microcephaly-micromelia syndrome (MIMIS) [MIM:251230] A severe autosomal recessive disorder characterized by intrauterine growth restriction, marked microcephaly, craniofacial anomalies, skeletal dysplasia, and variable malformations of the limbs, particularly the upper limbs. It usually results in death in utero or in the perinatal period. The disease is caused by variants affecting the gene represented in this entry. This extremely rare syndrome is caused by an intronic mutation that leads to the retention of intron 6, probably resulting in non-sense mediated mRNA decay. This isoform has also been detected in healthy tissues, but at much lower levels than in MIMIS samples. Microcephaly, short stature, and limb abnormalities (MISSLA) [MIM:617604] An autosomal recessive disorder characterized by intrauterine growth retardation, microcephaly, variable short stature, and limb abnormalities mainly affecting the upper limb and radial ray. Mild intellectual disability and developmental delay is observed in some patients. The disease is caused by variants affecting the gene represented in this entry.

Induction. Expression is cell-cycle dependent with highest levels during S phase.

Miscellaneous. May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay. May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.

Similarity. Belongs to the DONSON family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q9NYP3-1	1	yes
Q9NYP3-2	2
Q9NYP3-3	3

RefSeq proteins (1): NP_060083* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR024861	Donson	Family

UniProt features (27 total): sequence variant 14, splice variant 4, sequence conflict 3, compositionally biased region 2, modified residue 2, chain 1, region of interest 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9NYP3-F1	72.94	0.41

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 (2): 28, 34

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 284 (showing top): GOBP_DNA_TEMPLATED_DNA_REPLICATION_MAINTENANCE_OF_FIDELITY, RODRIGUES_THYROID_CARCINOMA_POORLY_DIFFERENTIATED_UP, GOBP_CELL_CYCLE_DNA_REPLICATION, GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_UP, GOBP_CELL_CYCLE_PHASE_TRANSITION, GCAAGGA_MIR502, GOBP_MITOTIC_G2_M_TRANSITION_CHECKPOINT, PATIL_LIVER_CANCER, GOBP_REGULATION_OF_CELL_CYCLE_G2_M_PHASE_TRANSITION, GOBP_NEGATIVE_REGULATION_OF_CELL_CYCLE_PROCESS, MOLENAAR_TARGETS_OF_CCND1_AND_CDK4_DN, GOBP_NEGATIVE_REGULATION_OF_CELL_CYCLE, BLALOCK_ALZHEIMERS_DISEASE_UP, BILD_E2F3_ONCOGENIC_SIGNATURE, GOBP_REGULATION_OF_CELL_CYCLE

GO Biological Process (6): DNA damage checkpoint signaling (GO:0000077), DNA replication (GO:0006260), mitotic G2 DNA damage checkpoint signaling (GO:0007095), replication fork processing (GO:0031297), nuclear DNA replication (GO:0033260), mitotic DNA replication checkpoint signaling (GO:0033314)

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

GO Cellular Component (3): nucleus (GO:0005634), replication fork (GO:0005657), replisome (GO:0030894)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
mitotic G2/M transition checkpoint	2
DNA integrity checkpoint signaling	1
signal transduction in response to DNA damage	1
DNA metabolic process	1
DNA biosynthetic process	1
mitotic G2 phase	1
mitotic DNA damage checkpoint signaling	1
DNA-templated DNA replication maintenance of fidelity	1
nucleus	1
cell cycle	1
cell cycle DNA replication	1
DNA replication checkpoint signaling	1
mitotic cell cycle	1
mitotic DNA integrity checkpoint signaling	1
binding	1
intracellular membrane-bounded organelle	1
chromosome	1
cellular anatomical structure	1
replication fork	1
protein-DNA complex	1
DNA helicase complex	1
DNA polymerase complex	1

Protein interactions and networks

STRING

1412 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
DONSON	GART	P22102	931
DONSON	SON	P18583	773
DONSON	SMARCA1	P28370	663
DONSON	TMEM50B	P56557	641
DONSON	EVA1C	P58658	582
DONSON	MRPS6	P82932	559
DONSON	CHAF1B	Q13112	537
DONSON	HEMK2	Q9Y5N5	521
DONSON	POFUT2	Q9Y2G5	521
DONSON	FANCM	Q8IYD8	517
DONSON	CCDC150	Q8NCX0	487
DONSON	SOX4	Q06945	469
DONSON	PDXK	O00764	464
DONSON	CRYZL1	O95825	464
DONSON	POLD2	P49005	452

IntAct

20 interactions, top by confidence:

A	B	Type	Score
DONSON	MCM2	psi-mi:“MI:2364”(proximity)	0.630
MCM2	DONSON	psi-mi:“MI:2364”(proximity)	0.630
DONSON	MCM2	psi-mi:“MI:0915”(physical association)	0.630
DONSON	MCM2	psi-mi:“MI:0914”(association)	0.630
MCM2	DONSON	psi-mi:“MI:0915”(physical association)	0.630
GINS1	CDC45	psi-mi:“MI:0914”(association)	0.620
GINS1	DONSON	psi-mi:“MI:2364”(proximity)	0.580
DONSON	GINS1	psi-mi:“MI:0915”(physical association)	0.580
DONSON	CDC45	psi-mi:“MI:0914”(association)	0.500
MCM5	DONSON	psi-mi:“MI:2364”(proximity)	0.500
CDC45	DONSON	psi-mi:“MI:2364”(proximity)	0.500
GINS1	MCM2	psi-mi:“MI:0914”(association)	0.350
PSMG1	PSMD1	psi-mi:“MI:0914”(association)	0.350
DONSON	HSP90AA5P	psi-mi:“MI:0914”(association)	0.350

BioGRID (45): DONSON (Affinity Capture-RNA), DONSON (Affinity Capture-MS), DONSON (Positive Genetic), DONSON (Positive Genetic), DONSON (Negative Genetic), DONSON (Positive Genetic), GEMIN4 (Positive Genetic), GNL3L (Negative Genetic), MED17 (Positive Genetic), PELO (Negative Genetic), PITRM1 (Positive Genetic), PMF1 (Positive Genetic), RPL24 (Negative Genetic), TRA2B (Negative Genetic), VPS72 (Negative Genetic)

ESM2 similar proteins: A0A0D9SF12, A2A8T7, A6H7E2, A6NF36, A6NFA0, A6NI87, E1C7U0, P03246, P03247, P0DO92, P14355, P14683, Q0VG49, Q1HVF6, Q32LN6, Q3KPU7, Q3KSS3, Q4V7D2, Q4ZG55, Q5DU28, Q5JX69, Q5JX71, Q5R7E2, Q5U4U4, Q642A3, Q6NRW0, Q6P1U0, Q6P4J6, Q6P9N1, Q6PEX7, Q6X4T0, Q7L3B6, Q7SYV9, Q7T346, Q80Y73, Q8BJS8, Q8CF25, Q8IWB6, Q8N6T0, Q8NCU1

Diamond homologs: Q5U4U4, Q6P1U0, Q9NYP3, Q9QXP4, Q9VNA8

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	31
Likely pathogenic	12
Uncertain significance	128
Likely benign	96
Benign	17

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1069880	NM_017613.4(DONSON):c.1324C>T (p.Arg442Ter)	Pathogenic
1098401	NM_017613.4(DONSON):c.1086_1087dup (p.Ser363fs)	Pathogenic
1173053	NM_017613.4(DONSON):c.631C>T (p.Arg211Cys)	Pathogenic
1173054	NM_017613.4(DONSON):c.1634C>T (p.Pro545Leu)	Pathogenic
1173062	NM_017613.4(DONSON):c.607-36G>A	Pathogenic
1410377	NM_017613.4(DONSON):c.1433C>T (p.Pro478Leu)	Pathogenic
1441615	NM_017613.4(DONSON):c.1367_1368del (p.Val456fs)	Pathogenic
1451531	NM_017613.4(DONSON):c.1563+1del	Pathogenic
1451926	NM_017613.4(DONSON):c.41dup (p.Pro15fs)	Pathogenic
1687665	NM_017613.4(DONSON):c.877C>T (p.Arg293Ter)	Pathogenic
1936222	NM_017613.4(DONSON):c.1142dup (p.Ile382fs)	Pathogenic
1937858	NM_017613.4(DONSON):c.1313_1314del (p.Pro438fs)	Pathogenic
2098376	NM_017613.4(DONSON):c.1487dup (p.Ser497fs)	Pathogenic
2105394	NM_017613.4(DONSON):c.1324del (p.Arg442fs)	Pathogenic
2222598	NM_017613.4(DONSON):c.916del (p.Leu306fs)	Pathogenic
2572996	NM_017613.4(DONSON):c.129_144dup (p.Leu49fs)	Pathogenic
2801729	NM_017613.4(DONSON):c.1253_1254del (p.Asn417_Ser418insTer)	Pathogenic
2832713	NM_017613.4(DONSON):c.744G>A (p.Trp248Ter)	Pathogenic
2875690	NM_017613.4(DONSON):c.1375_1376del (p.Gln459fs)	Pathogenic
3384067	NM_017613.4(DONSON):c.671_681del (p.Pro224fs)	Pathogenic
3638160	NM_017613.4(DONSON):c.995_996insT (p.Glu332fs)	Pathogenic
3647468	NM_017613.4(DONSON):c.1490_1491del (p.Ser497fs)	Pathogenic
3647959	NM_017613.4(DONSON):c.484C>T (p.Arg162Ter)	Pathogenic
3669624	NM_017613.4(DONSON):c.1411del (p.Glu471fs)	Pathogenic
431414	NM_017613.4(DONSON):c.1047-9A>G	Pathogenic
431415	NM_017613.4(DONSON):c.1337T>C (p.Met446Thr)	Pathogenic
431418	NM_017613.4(DONSON):c.1251_1256del (p.Asn417_Ser418del)	Pathogenic
4531765	NM_017613.4(DONSON):c.557_561del (p.Leu186fs)	Pathogenic
4813618	DONSON, PRO433SER	Pathogenic
488493	NM_017613.4(DONSON):c.683G>A (p.Trp228Ter)	Pathogenic

SpliceAI

1825 predictions. Top by Δscore:

Variant	Effect	Δscore
21:33579345:CTT:C	donor_loss	1.0000
21:33579346:TTA:T	donor_loss	1.0000
21:33579347:TACCA:T	donor_loss	1.0000
21:33579348:A:AC	donor_gain	1.0000
21:33579348:AC:A	donor_gain	1.0000
21:33579349:C:A	donor_loss	1.0000
21:33579349:C:CC	donor_gain	1.0000
21:33579349:CC:C	donor_gain	1.0000
21:33579349:CCAT:C	donor_gain	1.0000
21:33579349:CCATA:C	donor_gain	1.0000
21:33579566:CA:C	acceptor_gain	1.0000
21:33579567:A:AC	acceptor_gain	1.0000
21:33579567:A:C	acceptor_gain	1.0000
21:33579573:A:AC	acceptor_gain	1.0000
21:33579573:A:C	acceptor_gain	1.0000
21:33581950:CAG:C	donor_gain	1.0000
21:33582163:A:AC	donor_gain	1.0000
21:33582163:ACT:A	donor_gain	1.0000
21:33582163:ACTC:A	donor_gain	1.0000
21:33582163:ACTCC:A	donor_gain	1.0000
21:33582164:C:CC	donor_gain	1.0000
21:33582164:CT:C	donor_gain	1.0000
21:33582164:CTC:C	donor_gain	1.0000
21:33582164:CTCC:C	donor_gain	1.0000
21:33582164:CTCCC:C	donor_gain	1.0000
21:33582166:C:CA	donor_gain	1.0000
21:33582167:C:A	donor_gain	1.0000
21:33586015:CAATG:C	donor_gain	1.0000
21:33586042:T:TA	donor_gain	1.0000
21:33586179:AGTC:A	acceptor_loss	1.0000

AlphaMissense

3648 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
21:33584591:A:G	W262R	0.997
21:33584591:A:T	W262R	0.997
21:33581329:G:C	F441L	0.996
21:33581329:G:T	F441L	0.996
21:33581331:A:G	F441L	0.996
21:33586115:A:G	W157R	0.996
21:33586115:A:T	W157R	0.996
21:33583507:T:A	R315S	0.995
21:33583507:T:G	R315S	0.995
21:33583538:G:T	A305D	0.995
21:33586067:A:G	W173R	0.994
21:33586067:A:T	W173R	0.994
21:33581348:A:T	L435H	0.993
21:33581354:G:C	P433R	0.993
21:33581457:A:G	S399P	0.993
21:33583577:A:G	F292S	0.993
21:33583657:G:C	S265R	0.993
21:33583657:G:T	S265R	0.993
21:33583659:T:G	S265R	0.993
21:33584714:A:G	W221R	0.993
21:33584714:A:T	W221R	0.993
21:33579493:C:G	G474R	0.992
21:33581348:A:C	L435R	0.992
21:33581472:C:G	D394H	0.992
21:33583523:G:T	T310K	0.992
21:33584675:G:T	R234S	0.992
21:33581348:A:G	L435P	0.991
21:33581360:A:G	L431P	0.991
21:33586110:A:C	S158R	0.991
21:33586110:A:T	S158R	0.991

dbSNP variants (sampled 300 via entrez): RS1000162766 (21:33578202 T>TA), RS1000164987 (21:33588282 G>A,C), RS1000384402 (21:33585841 G>A,C), RS1000604263 (21:33579753 A>C), RS1000681745 (21:33578560 T>G), RS1000709479 (21:33580210 C>G), RS1001600906 (21:33584052 T>A,C), RS1001604121 (21:33585428 A>C,G), RS1001632213 (21:33585638 C>G,T), RS1001811752 (21:33579255 A>G), RS1001935887 (21:33585531 G>A,C), RS1001988706 (21:33585254 T>C), RS1002337441 (21:33580781 C>G), RS1002453914 (21:33579390 A>T), RS1002665870 (21:33582348 A>G)

Disease associations

OMIM: gene MIM:611428 | disease phenotypes: MIM:224690, MIM:617604, MIM:251230

GenCC curated gene-disease

Disease	Classification	Inheritance
microcephaly, short stature, and limb abnormalities	Strong	Autosomal recessive
microcephaly-micromelia syndrome	Strong	Autosomal recessive

Mondo (6): Meier-Gorlin syndrome (MONDO:0016817), microcephaly, short stature, and limb abnormalities (MONDO:0060533), Meier-Gorlin syndrome 1 (MONDO:0009143), microcephaly (MONDO:0001149), microcephaly-micromelia syndrome (MONDO:0009619), DONSON-related microcephaly-short stature-limb abnormalities spectrum (MONDO:0035534)

Orphanet (4): Ear-patella-short stature syndrome (Orphanet:2554), Microcephaly-short stature-limb abnormalities syndrome (Orphanet:572773), Microcephaly-micromelia syndrome (Orphanet:572768), DONSON-related microcephaly-short stature-limb abnormalities spectrum (Orphanet:572761)

HPO phenotypes

46 total (30 of 46 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000160	Narrow mouth
HP:0000175	Cleft palate
HP:0000252	Microcephaly
HP:0000347	Micrognathia
HP:0000369	Low-set ears
HP:0000444	Convex nasal ridge
HP:0000445	Wide nose
HP:0000470	Short neck
HP:0000476	Cystic hygroma
HP:0000568	Microphthalmia
HP:0000582	Upslanted palpebral fissure
HP:0000774	Narrow chest
HP:0000878	11 pairs of ribs
HP:0000921	Missing ribs
HP:0001156	Brachydactyly
HP:0001256	Mild intellectual disability
HP:0001263	Global developmental delay
HP:0001363	Craniosynostosis
HP:0001511	Intrauterine growth retardation
HP:0001562	Oligohydramnios
HP:0001762	Talipes equinovarus
HP:0002089	Pulmonary hypoplasia
HP:0002410	Aqueductal stenosis
HP:0002750	Delayed skeletal maturation
HP:0002974	Radioulnar synostosis
HP:0002983	Micromelia
HP:0002984	Hypoplasia of the radius
HP:0003027	Mesomelia
HP:0003041	Humeroradial synostosis

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST006804_105	Red cell distribution width	2.000000e-19

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0009188	Red cell distribution width

MeSH disease descriptors (3)

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
C538012	Meier-Gorlin syndrome (supp.)
C565382	Microcephaly-Micromelia Syndrome (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Aflatoxin B1	affects expression, increases expression	3
bisphenol A	decreases expression, increases methylation	2
sodium arsenite	increases expression	2
Cisplatin	increases expression, increases reaction	2
Doxorubicin	affects response to substance, decreases expression	2
Tobacco Smoke Pollution	increases expression	2
Valproic Acid	affects expression, increases expression	2
afuresertib	decreases expression	1
FR900359	affects phosphorylation	1
dicrotophos	decreases expression	1
beta-lapachone	increases expression	1
benzo(e)pyrene	decreases methylation	1
2,3-bis(3’-hydroxybenzyl)butyrolactone	affects cotreatment, increases expression	1
methacrylaldehyde	affects cotreatment, increases oxidation	1
perfluorooctane sulfonic acid	decreases expression	1
palbociclib	decreases expression	1
bisphenol S	affects cotreatment, decreases expression	1
Resveratrol	affects cotreatment, increases expression	1
Sunitinib	decreases expression	1
Acrolein	affects cotreatment, increases oxidation	1
Benzo(a)pyrene	increases expression	1
Caffeine	decreases phosphorylation	1
Calcitriol	decreases expression, affects cotreatment	1
Coumestrol	affects cotreatment, increases expression	1
Demecolcine	decreases expression	1
Dexamethasone	affects cotreatment, decreases expression	1
Endosulfan	increases expression	1
Estradiol	increases expression	1
Indomethacin	affects cotreatment, decreases expression	1
Methapyrilene	decreases methylation	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT04569149	Not specified	RECRUITING	Primordial Dwarfism Registry
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.