KIFBP

Summary

KIFBP (kinesin family binding protein, HGNC:23419) is a protein-coding gene on chromosome 10q22.1, encoding KIF-binding protein (Q96EK5). Activator of KIF1B plus-end-directed microtubule motor activity.

This gene encodes a kinesin family member 1 binding protein that is characterized by two tetratrico peptide repeats. The encoded protein localizes to the mitochondria and may be involved in regulating transport of the mitochondria. Mutations in this gene are associated with Goldberg-Shprintzen megacolon syndrome.

Source: NCBI Gene 26128 — RefSeq curated summary.

At a glance

• Gene–disease (curated): Goldberg-Shprintzen syndrome (Definitive, ClinGen)
• Clinical variants (ClinVar): 251 total — 10 pathogenic, 5 likely-pathogenic
• Phenotypes (HPO): 58
• Dosage sensitivity (ClinGen): haploinsufficiency autosomal recessive, triplosensitivity unscored
• MANE Select transcript: NM_015634

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:23419
Approved symbol	KIFBP
Name	kinesin family binding protein
Location	10q22.1
Locus type	gene with protein product
Status	Approved
Aliases	DKFZP586B0923, TTC20, KBP
Ensembl gene	ENSG00000198954
Ensembl biotype	protein_coding
OMIM	609367
Entrez	26128

Gene structure

Transcript identifiers

Ensembl transcripts: 21 — 9 protein_coding, 8 nonsense_mediated_decay, 3 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000361983, ENST00000481912, ENST00000625461, ENST00000626493, ENST00000627949, ENST00000635779, ENST00000635971, ENST00000636200, ENST00000637101, ENST00000637104, ENST00000637323, ENST00000637420, ENST00000637738, ENST00000638119, ENST00000674660, ENST00000674688, ENST00000674897, ENST00000674936, ENST00000675576, ENST00000676080, ENST00000938815

RefSeq mRNA: 1 — MANE Select: NM_015634 NM_015634

CCDS: CCDS7284

Canonical transcript exons

ENST00000361983 — 7 exons

Exon	Start	End
ENSE00000986268	69000424	69000522
ENSE00001095958	69005046	69005125
ENSE00001095963	69005732	69005915
ENSE00001460618	69015541	69016982
ENSE00003536325	69010900	69011015
ENSE00003632969	69008841	69008925
ENSE00003843318	68988803	68989258

Expression profiles

Bgee: expression breadth ubiquitous, 291 present calls, max score 94.84.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 23.3240 / max 301.4259, expressed in 1796 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
105283	23.3240	1796

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
frontal pole	UBERON:0002795	94.84	gold quality
ventricular zone	UBERON:0003053	94.83	gold quality
secondary oocyte	CL:0000655	94.76	gold quality
paraflocculus	UBERON:0005351	94.41	gold quality
heart right ventricle	UBERON:0002080	94.19	gold quality
middle frontal gyrus	UBERON:0002702	94.07	gold quality
prefrontal cortex	UBERON:0000451	93.92	gold quality
oocyte	CL:0000023	93.50	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	93.39	gold quality
ganglionic eminence	UBERON:0004023	93.21	gold quality
Brodmann (1909) area 9	UBERON:0013540	93.11	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	92.89	gold quality
orbitofrontal cortex	UBERON:0004167	92.51	gold quality
frontal cortex	UBERON:0001870	92.44	gold quality
cerebellar cortex	UBERON:0002129	92.42	gold quality
cerebellar hemisphere	UBERON:0002245	92.37	gold quality
cerebellar vermis	UBERON:0004720	92.25	gold quality
cerebellum	UBERON:0002037	92.23	gold quality
islet of Langerhans	UBERON:0000006	92.22	gold quality
neocortex	UBERON:0001950	92.15	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	92.09	gold quality
pons	UBERON:0000988	92.07	gold quality
Brodmann (1909) area 10	UBERON:0013541	92.04	gold quality
cingulate cortex	UBERON:0003027	91.91	gold quality
anterior cingulate cortex	UBERON:0009835	91.88	gold quality
right frontal lobe	UBERON:0002810	91.83	gold quality
right hemisphere of cerebellum	UBERON:0014890	91.82	gold quality
spinal cord	UBERON:0002240	91.78	gold quality
cortical plate	UBERON:0005343	91.74	gold quality
heart left ventricle	UBERON:0002084	91.73	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	6.11
E-MTAB-7303	no	193.42

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AP1, ATF3, E2F4, E2F6, EZH2, HR, IRF6, JUN, NFKB1, NFKB, SP1, SP3, TP53

miRNA regulators (miRDB)

43 targeting KIFBP, 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-1277-5P	100.00	73.95	5056
HSA-MIR-223-3P	99.99	70.14	1140
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-32-5P	99.98	75.21	1964
HSA-MIR-92A-3P	99.98	75.21	1960
HSA-MIR-92B-3P	99.98	75.25	1955
HSA-MIR-25-3P	99.98	74.60	1817
HSA-MIR-363-3P	99.98	74.72	1821
HSA-MIR-367-3P	99.98	74.83	1819
HSA-MIR-1305	99.91	71.43	3443
HSA-MIR-5680	99.91	69.83	3421
HSA-MIR-374A-5P	99.90	71.34	2923
HSA-MIR-374B-5P	99.90	69.98	2734
HSA-MIR-4496	99.88	68.89	2236
HSA-MIR-5003-3P	99.85	69.29	2517
HSA-MIR-6739-5P	99.80	67.87	2806
HSA-MIR-6733-5P	99.74	67.94	2759
HSA-MIR-548M	99.70	68.87	1749
HSA-MIR-4328	99.57	71.06	4094
HSA-MIR-3153	99.55	67.59	2337
HSA-MIR-302B-5P	99.50	69.49	1857
HSA-MIR-302D-5P	99.50	69.34	1863
HSA-MIR-5584-5P	99.49	68.22	2814
HSA-MIR-32-3P	99.36	68.20	2517
HSA-MIR-3606-5P	99.31	69.67	1168
HSA-MIR-4279	99.19	66.70	2437
HSA-MIR-499A-3P	99.18	69.20	1392
HSA-MIR-499B-3P	99.18	69.27	1391
HSA-MIR-7109-5P	99.18	66.13	1057
HSA-MIR-4742-3P	98.73	69.82	1803

Functional genomics

ClinGen dosage: haploinsufficiency 30 (autosomal recessive), triplosensitivity Not yet evaluated (unscored). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 9)

• KBP is a new binding partner for KIF1Balpha that is a regulator of its transport function and thus represents a new type of kinesin interacting protein. (PMID:16225668)
• KBP-cytoskeleton interactions is involved in neuronal development in Goldberg-Shprintzen syndrome. (PMID:23427148)
• A report on fetal cases with a homozygous mutation in KBP gene in a consanguineous Pakistani family with isolated polymicrogyria. (PMID:24072599)
• Data suggest that KBP functions as a kinesin inhibitor that modulates MT-based cargo motility and depolymerizing activity of a subset of kinesin motors. We propose that misregulation of KBP-controlled kinesin motors may represent the underlying molecular mechanism that contributes to the neuropathological defects observed in Goldberg-Shprintzen syndrome patients. (PMID:26948876)
• Both Kif15 and KBP are required for the alignment of all the chromosomes to the metaphase plate and the assembly of stable kinetochore fibers of the correct length. (PMID:28445502)
• KBP acts as a protein buffer in mitosis, protecting cells from excessive KIF18A and KIF15 activity to promote accurate chromosome segregation. (PMID:30709852)
• Goldberg-Shprintzen syndrome is determined by the absence, or reduced expression levels, of KIFBP. (PMID:32939943)
• The mechanism of kinesin inhibition by kinesin-binding protein. (PMID:33252036)
• Progressive ataxia, ophthalmoparesis, and hypogonadotropic hypogonadism in a family with a novel variant in the KIFBP gene. (PMID:37903629)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	kifbp	ENSDARG00000062053
mus_musculus	Kifbp	ENSMUSG00000036955
rattus_norvegicus	Kifbp	ENSRNOG00000000395
drosophila_melanogaster	CG14043	FBGN0031659

Protein

Protein identifiers

KIF-binding protein — Q96EK5 (reviewed: Q96EK5)

Alternative names: KIF1-binding protein, Kinesin family binding protein

All UniProt accessions (15): Q96EK5, A0A0D9SFK7, A0A1B0GTE2, A0A1B0GTE6, A0A1B0GTX3, A0A1B0GU96, A0A1B0GUA3, A0A1B0GUH6, A0A1B0GVY9, A0A1B0GW21, A0A6Q8PGG2, A0A6Q8PH08, A0A6Q8PH45, A0A6Q8PHE6, A0A6Q8PHL8

UniProt curated annotations — full annotation on UniProt →

Function. Activator of KIF1B plus-end-directed microtubule motor activity. Required for organization of axonal microtubules, and axonal outgrowth and maintenance during peripheral and central nervous system development.

Subunit / interactions. Interacts with KIF1B; positively regulates KIF1B microtubule motor activity. Interacts with STMN2.

Subcellular location. Cytoplasm. Cytoskeleton.

Tissue specificity. Highly expressed in heart, brain, ovary, testis, spinal cord and all specific brain regions examined. Moderate expressed at intermediate level in all other adult tissues examined, as well as in fetal liver and brain. Not expressed in blood leukocytes.

Disease relevance. Goldberg-Shprintzen syndrome (GOSHS) [MIM:609460] A disorder characterized by intellectual disability, microcephaly, and dysmorphic facial features. Most patients also have Hirschsprung disease. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the KIF-binding protein family.

RefSeq proteins (1): NP_056449* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR011990	TPR-like_helical_dom_sf	Homologous_superfamily
IPR022083	KBP	Family

Pfam: PF12309

UniProt features (8 total): sequence conflict 3, chain 1, region of interest 1, compositionally biased region 1, modified residue 1, sequence variant 1

Structure

Experimental structures (PDB)

6 structures.

PDB	Method	Resolution (Å)
7RSQ	ELECTRON MICROSCOPY	3.8
6ZPG	ELECTRON MICROSCOPY	4.6
7RYQ	ELECTRON MICROSCOPY	4.6
7RYP	ELECTRON MICROSCOPY	4.8
7RSI	ELECTRON MICROSCOPY	4.9
6ZPH	ELECTRON MICROSCOPY	6.9

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96EK5-F1	90.76	0.81

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 (1): 178

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 276 (showing top): BORCZUK_MALIGNANT_MESOTHELIOMA_UP, GOBP_EMBRYO_DEVELOPMENT_ENDING_IN_BIRTH_OR_EGG_HATCHING, GOBP_NEUROGENESIS, GOBP_ORGANELLE_TRANSPORT_ALONG_MICROTUBULE, GOBP_IN_UTERO_EMBRYONIC_DEVELOPMENT, TGIF_01, GOBP_CENTRAL_NERVOUS_SYSTEM_NEURON_DIFFERENTIATION, GOBP_CENTRAL_NERVOUS_SYSTEM_PROJECTION_NEURON_AXONOGENESIS, LASTOWSKA_NEUROBLASTOMA_COPY_NUMBER_DN, MARTINEZ_RESPONSE_TO_TRABECTEDIN_DN, GOBP_EMBRYO_DEVELOPMENT, GOBP_CELL_PROJECTION_ORGANIZATION, MEDINA_SMARCA4_TARGETS, GOBP_MITOCHONDRION_LOCALIZATION, GOBP_CENTRAL_NERVOUS_SYSTEM_NEURON_DEVELOPMENT

GO Biological Process (8): microtubule cytoskeleton organization (GO:0000226), in utero embryonic development (GO:0001701), transport along microtubule (GO:0010970), central nervous system projection neuron axonogenesis (GO:0021952), mitochondrion transport along microtubule (GO:0047497), neuron projection maintenance (GO:1990535), nervous system development (GO:0007399), cell differentiation (GO:0030154)

GO Molecular Function (3): kinesin binding (GO:0019894), protein sequestering activity (GO:0140311), protein binding (GO:0005515)

GO Cellular Component (3): mitochondrion (GO:0005739), cytoskeleton (GO:0005856), cytoplasm (GO:0005737)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cytoskeleton organization	1
microtubule-based process	1
chordate embryonic development	1
microtubule-based movement	1
cytoskeleton-dependent intracellular transport	1
microtubule-based transport	1
central nervous system neuron axonogenesis	1
establishment of mitochondrion localization, microtubule-mediated	1
organelle transport along microtubule	1
neuron projection organization	1
system development	1
cellular developmental process	1
cytoskeletal protein binding	1
protein binding	1
molecular sequestering activity	1
binding	1
cytoplasm	1
intracellular membrane-bounded organelle	1
intracellular membraneless organelle	1
intracellular anatomical structure	1
cellular anatomical structure	1

Protein interactions and networks

STRING

478 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
KIFBP	KIF1C	O43896	888
KIFBP	KIF1B	O60333	810
KIFBP	KIF15	Q9NS87	720
KIFBP	ZEB2	O60315	646
KIFBP	RET	P07949	537
KIFBP	TRAK1	Q9UPV9	520
KIFBP	KTN1	Q86UP2	511
KIFBP	PHOX2B	Q99453	445
KIFBP	RAB3GAP1	Q15042	432
KIFBP	DISC1	Q9NRI5	429
KIFBP	NRTN	Q99748	419
KIFBP	KIF5C	O60282	419
KIFBP	TRAK2	O60296	415
KIFBP	EDN3	P14138	400
KIFBP	ECE1	P42892	395

IntAct

115 interactions, top by confidence:

A	B	Type	Score
BBS1	BBS9	psi-mi:“MI:0914”(association)	0.940
ANKRD54	TULP3	psi-mi:“MI:0914”(association)	0.930
GORASP2	GOLGA2	psi-mi:“MI:0914”(association)	0.880
RFXANK	RFXAP	psi-mi:“MI:0914”(association)	0.780
PPP1CC	CCDC85C	psi-mi:“MI:0914”(association)	0.740
KIF3A	KIF3C	psi-mi:“MI:0914”(association)	0.730
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
PPP1CA	CCDC85C	psi-mi:“MI:0914”(association)	0.670
FAM90A1	KPNA3	psi-mi:“MI:0914”(association)	0.670
DHRS13	KIFBP	psi-mi:“MI:0915”(physical association)	0.640
TIGD4	KIFBP	psi-mi:“MI:0915”(physical association)	0.590
SAV1	SEC16A	psi-mi:“MI:2364”(proximity)	0.570
KIFBP	DCTN1	psi-mi:“MI:0915”(physical association)	0.560
KIFBP	DOK2	psi-mi:“MI:0915”(physical association)	0.550
DOK2	KIFBP	psi-mi:“MI:0915”(physical association)	0.550
KIFBP	KIF3C	psi-mi:“MI:0914”(association)	0.530
VPS37D	CRTAP	psi-mi:“MI:0914”(association)	0.530
CCDC89	ZMYM6	psi-mi:“MI:0914”(association)	0.530
ILK	ILVBL	psi-mi:“MI:0914”(association)	0.530
PTGES3	AIP	psi-mi:“MI:0914”(association)	0.530

BioGRID (234): KIAA1279 (Affinity Capture-MS), KIAA1279 (Affinity Capture-MS), KIAA1279 (Affinity Capture-MS), KIAA1279 (Affinity Capture-MS), KIAA1279 (Affinity Capture-MS), KIAA1279 (Affinity Capture-MS), KIAA1279 (Affinity Capture-MS), CEP76 (Two-hybrid), KIAA1279 (Two-hybrid), ZNF638 (Two-hybrid), ZNF670 (Two-hybrid), KIAA1279 (Two-hybrid), PLEKHF1 (Two-hybrid), KIAA1279 (Two-hybrid), KIAA1279 (Affinity Capture-Western)

ESM2 similar proteins: A0MT11, A1Z3X3, A2VD00, A4GWN3, A4II09, A4QNE0, A4VCH4, B5KFI0, O35841, P48553, P49754, Q09161, Q0P5I8, Q15386, Q3TLI0, Q3UYV9, Q56A27, Q5E9L7, Q5KU39, Q5R644, Q5XI83, Q5ZJZ6, Q5ZKG8, Q5ZMW3, Q640V2, Q6GLK9, Q6GLP4, Q6N069, Q6NRL4, Q6TGY8, Q6WKZ8, Q7L5D6, Q7ZY79, Q80U95, Q80UM3, Q80YQ8, Q8BWQ6, Q8IWV8, Q8VZM1, Q91W86

Diamond homologs: A8WE67, Q0IIZ5, Q3SYS9, Q4G074, Q5ZIL9, Q6ZPU9, Q96EK5, Q9VMX1

SIGNOR signaling

0 interactions.

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.

GO biological processes:

GO term	Partners	Fold	FDR
protein folding	9	7.8×	2e-03
protein stabilization	10	5.6×	5e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	10
Likely pathogenic	5
Uncertain significance	148
Likely benign	46
Benign	20

Top pathogenic / likely-pathogenic (15)

Variant ID	HGVS	Classification
1299541	NM_015634.4(KIFBP):c.1176_1177del (p.Glu394fs)	Pathogenic
1299542	NM_015634.4(KIFBP):c.1535C>G (p.Ser512Ter)	Pathogenic
1694469	NM_015634.4(KIFBP):c.128_132dup (p.Glu45fs)	Pathogenic
1733	NM_015634.4(KIFBP):c.268C>T (p.Arg90Ter)	Pathogenic
1734	NM_015634.4(KIFBP):c.250G>T (p.Glu84Ter)	Pathogenic
183145	NM_015634.4(KIFBP):c.599C>A (p.Ser200Ter)	Pathogenic
183146	NM_015634.4(KIFBP):c.605_606del (p.Arg202fs)	Pathogenic
183147	NC_000010.11:g.(68989259_69000424)_(69005125_69005731)del	Pathogenic
3896359	NM_015634.4(KIFBP):c.1353_1354del (p.Ala452fs)	Pathogenic
437448	NM_015634.4(KIFBP):c.976C>T (p.Gln326Ter)	Pathogenic
1928542	NM_015634.4(KIFBP):c.605+1G>A	Likely pathogenic
2584999	NM_015634.4(KIFBP):c.108del (p.Lys36fs)	Likely pathogenic
3381947	NM_015634.4(KIFBP):c.616del (p.Val206fs)	Likely pathogenic
974776	NM_015634.4(KIFBP):c.169G>T (p.Glu57Ter)	Likely pathogenic
988582	NM_015634.4(KIFBP):c.1723del (p.His575fs)	Likely pathogenic

SpliceAI

1233 predictions. Top by Δscore:

Variant	Effect	Δscore
10:69000415:A:AG	acceptor_gain	1.0000
10:69000416:T:G	acceptor_gain	1.0000
10:69000420:CCAG:C	acceptor_loss	1.0000
10:69000421:CA:C	acceptor_loss	1.0000
10:69000422:A:AG	acceptor_gain	1.0000
10:69000422:AGAA:A	acceptor_loss	1.0000
10:69000423:G:GA	acceptor_gain	1.0000
10:69000423:GA:G	acceptor_gain	1.0000
10:69000423:GAA:G	acceptor_gain	1.0000
10:69000423:GAAT:G	acceptor_gain	1.0000
10:69000423:GAATA:G	acceptor_gain	1.0000
10:69000520:GAG:G	donor_gain	1.0000
10:69000521:AGGTA:A	donor_loss	1.0000
10:69000522:GGTA:G	donor_loss	1.0000
10:69000523:G:GA	donor_loss	1.0000
10:69005038:A:AG	acceptor_gain	1.0000
10:69005039:A:G	acceptor_gain	1.0000
10:69005041:T:A	acceptor_gain	1.0000
10:69005042:GTA:G	acceptor_loss	1.0000
10:69005044:A:AG	acceptor_gain	1.0000
10:69005044:AG:A	acceptor_gain	1.0000
10:69005044:AGGTT:A	acceptor_gain	1.0000
10:69005045:G:GC	acceptor_gain	1.0000
10:69005045:GG:G	acceptor_gain	1.0000
10:69005045:GGT:G	acceptor_gain	1.0000
10:69005045:GGTT:G	acceptor_gain	1.0000
10:69005045:GGTTG:G	acceptor_gain	1.0000
10:69005121:AAAAG:A	donor_gain	1.0000
10:69005122:AAAG:A	donor_gain	1.0000
10:69005123:AAG:A	donor_gain	1.0000

AlphaMissense

4089 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
10:69005767:T:C	L214P	1.000
10:69005830:T:C	L235P	1.000
10:69005836:G:C	R237P	1.000
10:69005871:T:A	W249R	1.000
10:69005871:T:C	W249R	1.000
10:69005873:G:C	W249C	1.000
10:69005873:G:T	W249C	1.000
10:69005883:G:C	A253P	1.000
10:69005887:C:A	A254D	1.000
10:68989136:G:T	G102W	0.999
10:68989137:G:A	G102E	0.999
10:68989172:G:T	G114W	0.999
10:68989173:G:A	G114E	0.999
10:69000433:G:C	G146R	0.999
10:69000434:G:A	G146D	0.999
10:69000470:C:A	A158E	0.999
10:69000482:T:C	L162P	0.999
10:69005760:T:G	Y212D	0.999
10:69005769:G:C	A215P	0.999
10:69005770:C:A	A215D	0.999
10:69005773:A:C	Q216P	0.999
10:69005809:C:A	A228D	0.999
10:69005819:C:G	C231W	0.999
10:69005839:A:C	Q238P	0.999
10:69005842:T:C	L239P	0.999
10:69005872:G:C	W249S	0.999
10:69005874:G:C	A250P	0.999
10:69005875:C:A	A250D	0.999
10:69005884:C:A	A253D	0.999
10:69005886:G:C	A254P	0.999

dbSNP variants (sampled 300 via entrez): RS1000108097 (10:69004977 C>G), RS1000140693 (10:69005250 C>T), RS1000217534 (10:68998504 T>C), RS1000252727 (10:68999034 G>A), RS1000277009 (10:69011169 G>A,T), RS1000388466 (10:68991519 A>C,G), RS1000525454 (10:69009892 TACAAATGG>T), RS1000708660 (10:69017039 C>T), RS1000829994 (10:69017350 C>T), RS1000982369 (10:69009644 T>A), RS1001179215 (10:69012805 A>G), RS1001318201 (10:69003377 T>C), RS1001370973 (10:68999385 A>C,G), RS1001417784 (10:69010759 T>C), RS1001485497 (10:68999608 C>G)

Disease associations

OMIM: gene MIM:609367 | disease phenotypes: MIM:609460

GenCC curated gene-disease

Disease	Classification	Inheritance
Goldberg-Shprintzen syndrome	Definitive	Autosomal recessive

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
Goldberg-Shprintzen syndrome	Definitive	AR

Mondo (3): Goldberg-Shprintzen syndrome (MONDO:0012280), epilepsy (MONDO:0005027), peripheral neuropathy (MONDO:0005244)

Orphanet (1): Goldberg-Shprintzen megacolon syndrome (Orphanet:66629)

HPO phenotypes

58 total (30 of 58 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000047	Hypospadias
HP:0000048	Bifid scrotum
HP:0000076	Vesicoureteral reflux
HP:0000175	Cleft palate
HP:0000232	Everted lower lip vermilion
HP:0000252	Microcephaly
HP:0000307	Pointed chin
HP:0000316	Hypertelorism
HP:0000322	Short philtrum
HP:0000327	Hypoplasia of the maxilla
HP:0000340	Sloping forehead
HP:0000369	Low-set ears
HP:0000400	Macrotia
HP:0000414	Bulbous nose
HP:0000426	Prominent nasal bridge
HP:0000431	Wide nasal bridge
HP:0000470	Short neck
HP:0000485	Megalocornea
HP:0000494	Downslanted palpebral fissures
HP:0000506	Telecanthus
HP:0000508	Ptosis
HP:0000540	Hypermetropia
HP:0000574	Thick eyebrow
HP:0000592	Blue sclerae
HP:0000612	Iris coloboma
HP:0000664	Synophrys
HP:0000677	Oligodontia
HP:0001182	Tapered finger
HP:0001249	Intellectual disability

GWAS associations

0 associations (top):

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D004827	Epilepsy	C10.228.140.490
C537279	Goldberg-Shprintzen megacolon syndrome (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

24 total (human), top 24 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression	2
Air Pollutants	affects cotreatment, increases abundance, increases oxidation, decreases expression	2
alpha-pinene	affects cotreatment, increases oxidation, increases abundance	1
methacrylaldehyde	affects cotreatment, increases oxidation, increases abundance	1
K 7174	increases expression	1
abrine	decreases expression	1
jinfukang	decreases expression	1
3-(2-hydroxy-4-(2-methylnonan-2-yl)phenyl)cyclohexan-1-ol	increases expression	1
Sunitinib	decreases expression	1
Acetaminophen	increases expression	1
Acrolein	affects cotreatment, increases oxidation, increases abundance	1
Caffeine	decreases phosphorylation	1
Ivermectin	decreases expression	1
Oxygen	decreases expression	1
Ozone	affects cotreatment, increases oxidation, increases abundance	1
Tamoxifen	affects expression	1
Thiram	decreases expression	1
Valproic Acid	affects expression	1
Cyclosporine	decreases expression	1
Asbestos, Crocidolite	decreases expression	1
Copper Sulfate	decreases expression	1
tert-Butylhydroperoxide	increases expression	1
Particulate Matter	decreases expression, increases abundance	1
Volatile Organic Compounds	increases oxidation, affects cotreatment	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00004637	PHASE4	COMPLETED	Double-Blind, Placebo-Controlled Trial of Vitamin E as Add-on Therapy for Children With Epilepsy
NCT00043914	PHASE4	COMPLETED	Measurement Of Serum Levels Of Two Antiepileptic Drugs During Conversion In Patients With Epilepsy
NCT00132223	PHASE4	UNKNOWN	Effects on the Diagnostic Accuracy of Magnetic Imaging Angiographies of the Supra-Aortic Vessels by Three Different Magnetic Resonance Contrast Agents in Patients
NCT00133081	PHASE4	UNKNOWN	Study to Improve the Treatment of Epilepsy (SITE)
NCT00137709	PHASE4	UNKNOWN	Hormone Profiles in Adults With Newly Diagnosed Epilepsy
NCT00154076	PHASE4	COMPLETED	A Multicenter Comparative Trial of Zonisamide and Topiramate as Initial Monotherapy in Untreated Epilepsies
NCT00165828	PHASE4	TERMINATED	Efficacy and Safety of an add-on Treatment With Zonisamide in Adults With Focal Epileptic Seizures With or Without Secondary Generalization
NCT00181116	PHASE4	COMPLETED	Levetiracetam for Benign Rolandic Epilepsy
NCT00207935	PHASE4	COMPLETED	Use of Sustained Release Antiepileptic Medication (Depakote® ER) for Pediatric Epilepsy in a Mental Retardation/Developmental Disorder Population
NCT00215592	PHASE4	COMPLETED	Open Label, Zonegran (Zonisamide) In Partial Onset Seizures
NCT00266604	PHASE4	COMPLETED	A Study to Evaluate the Dosing, Effectiveness and Safety of Topiramate for the Treatment of Epilepsy
NCT00288639	PHASE4	COMPLETED	Lyrica (Pregabalin) Administered as an Add-on Therapy for Partial Seizures (LEADER).
NCT00312676	PHASE4	UNKNOWN	Compare Tolerability of an Overnight Switch to Gradual Switch Between Two Different Forms of Depakote
NCT00323947	PHASE4	COMPLETED	Methylphenidate for Treating Attention Deficit Hyperactivity Disorder in Children With Both ADHD and Epilepsy
NCT00385411	PHASE4	COMPLETED	Study of Valproate in Young Patients Suffering From Epilepsy
NCT00522418	PHASE4	TERMINATED	Study Comparing Best Medical Practice With or Without VNS Therapy in Pharmacoresistant Partial Epilepsy Patients
NCT00537940	PHASE4	COMPLETED	Comparative Study Of Pregabalin And Gabapentin As Adjunctive Therapy In Subjects With Partial Seizures
NCT00552526	PHASE4	UNKNOWN	Ketogenic Diet vs.Antiepileptic Drug Treatment in Drug Resistant Epilepsy
NCT00564915	PHASE4	COMPLETED	RCT of the Efficacy of the Ketogenic Diet in the Treatment of Epilepsy
NCT00571155	PHASE4	COMPLETED	Trial of Levetiracetam in Patients With Primary Brain Tumors and Symptomatic Seizures Who Undergo Surgery
NCT00572195	PHASE4	COMPLETED	RNS® System LTT Study
NCT00610532	PHASE4	TERMINATED	Evaluating the Transporter Protein Inhibitor Probenecid In Patients With Epilepsy
NCT00630357	PHASE4	COMPLETED	Trial to Evaluate the Safety and Efficacy of Keppra After Conversion to Mono-therapy in Subjects With Partial Epilepsy
NCT00630630	PHASE4	COMPLETED	Study on Safety and Efficacy of Levetiracetam in the Adjunctive Treatment of Female Subjects With C1 Catamenial Epilepsy
NCT00630968	PHASE4	COMPLETED	S.K.A.T.E.: Safety of Keppra as Adjunctive Therapy in Epilepsy
NCT00631150	PHASE4	COMPLETED	A Phase IV-Pharmacovigilance Study of Keppra Greece - S.K.A.T.E.: Safety of Keppra as Adjunctive Therapy in Epilepsy
NCT00659958	PHASE4	COMPLETED	ZAGAL Study: Evaluating Effectiveness and Tolerability of Zonisamide as Adjunctive Therapy in Patients With Partial Onset Seizures Treated With Two Antiepileptic Drugs
NCT00713622	PHASE4	COMPLETED	Comparing The Effect On Cognition Of Adjunctive Therapy With Zonisamide Versus Sodium Valproate
NCT00807989	PHASE4	COMPLETED	The Efficacy and Safety of Low Dose Combination of LTG and VPA Compared to CBZ Monotherapy
NCT00832884	PHASE4	COMPLETED	The Safety of Intravenous Lacosamide
NCT00869622	PHASE4	COMPLETED	Antiepileptic Drugs and Osteoporotic Prevention Trial
NCT00896987	PHASE4	COMPLETED	Lamotrigine Cognitive Function Study in Adult Untreated Epilepsies
NCT00952081	PHASE4	COMPLETED	A Pilot Study to Evaluate Efficacy and Safety of Clevidipine in Neurosurgical Patients
NCT01118455	PHASE4	TERMINATED	Trial to Assess Vagus Nerve Stimulation Therapy vs. Anti-Epileptic Drug (AED) Treatment in Children With Refractory Seizures
NCT01127165	PHASE4	COMPLETED	Low and High Dose Zonisamide in Children as Monotherapy
NCT01127256	PHASE4	COMPLETED	Comparative Study of Zonisamide and Carbamazepine as an Initial Monotherapy: Efficacy and Safety Evaluation
NCT01140867	PHASE4	COMPLETED	Open-label, Multi-center Trial of Zonisamide as Adjunctive Therapy in Patients With Uncontrolled Partial Epilepsy
NCT01175954	PHASE4	COMPLETED	Cognitive and Behavioral Effects of Lacosamide
NCT01229735	PHASE4	COMPLETED	Levetiracetam Versus Topiramate as Adjunctive Therapy to Evaluate Efficacy and Safety in Subjects With Refractory Partial Onset Seizures
NCT01244724	PHASE4	TERMINATED	Lexapro for Major Depression in Patients With Epilepsy