Holoprosencephaly malady

NIH Rare Diseases: Holoprosencephaly is an abnormality of brain development that also affects the head and face. Normally, the brain divides into two halves (hemispheres) during early development. Holoprosencephaly occurs when the brain fails to divide properly into the right and left hemispheres. There are four types of holoprosencephaly according to the degree of brain division. From most to least severe, the types are known as alobar, semi-lobar, lobar, and middle interhemispheric variant (MIHV). The most severely affected individuals have one central eye (cyclopia) and a tubular nasal structure (proboscis) located above the eye. In the less severe forms, the brain is partially divided and the eyes are usually set close together (hypotelorism). Holoprosencephaly can be caused by mutations in a single gene, chromosome abnormalities, or substances that cause birth defects (teratogens).³⁰

MalaCards: Holoprosencephaly, also known as holoprosencephaly sequence (disorder), is related to holoprosencephaly, recurrent infections, and monocytosis and exencephaly. An important gene associated with Holoprosencephaly is SIX3 (SIX homeobox 3), and among its related pathways are Signaling by NODAL and Development_Hedgehog and PTH signaling pathways in bone and cartilage development. The compounds sant-2 and 20(s)-hydroxycholesterol have been mentioned in the context of this disorder. Affiliated tissues include brain, heart and t cells, and related mouse phenotypes are taste/olfaction and pigmentation.

NINDS: Holoprosencephaly is a disorder caused by the failure of the (the embryonic forebrain) to sufficiently divide into the double lobes of the cerebral hemispheres. The result is a single-lobed brain structure and severe skull and facial defects. In most cases of holoprosencephaly, the malformations are so severe that babies die before birth. In less severe cases, babies are born with normal or near-normal brain development and facial deformities that may affect the eyes, nose, and upper lip.³¹

Genetics Home Reference: Nonsyndromic holoprosencephaly is an abnormality of brain development that also affects the head and face. Normally, the brain divides into two halves (hemispheres) during early development. Holoprosencephaly occurs when the brain fails to divide properly into the right and left hemispheres. This condition is called nonsyndromic to distinguish it from other types of holoprosencephaly caused by genetic syndromes, chromosome abnormalities, or substances that cause birth defects (teratogens). The severity of nonsyndromic holoprosencephaly varies widely among affected individuals, even within the same family.¹⁷

Wikipedia: Holoprosencephaly (HPE, once known as arhinencephaly) is a cephalic disorder in which the prosencephalon...⁴⁴ more...

GeneReviews summary for hpe-overview

Aliases & Descriptions:

holoprosencephaly 6 7 15 30 16 31 8 32 holoprosencephaly sequence (disorder) 6

hpe 30

Disease types for holoprosencephaly family:

holoprosencephaly-1	holoprosencephaly-8

Diseases related to holoprosencephaly by text searches and GeneDecks gene sharing:

(show top 50)    (show all 101)

id	Related Disease	Score	Top Affiliating Genes
1	holoprosencephaly, recurrent infections, and monocytosis	30.4	SIX3, PTCH1, GLI2
2	exencephaly	29.2	TGIF1, HPE6, APOB
3	ectrodactyly	28.2	SIX3, DHCR7, TGIF1, GLI2, FGF8
4	situs ambiguus	28.1	SHH, NODAL, MNX1
5	moyamoya disease	28.1	SIX3, TGIF1, SHH, ZIC2
6	polydactyly	27.5	BMP4, ZIC2, UBTD2, MNX1, FGF8, FBXW11
7	cleft lip	27.1	SIX3, PRRX1, DHCR7, TGIF1, SHH, PTER
8	smith-lemli-opitz syndrome	26.8	DHCR7, SHH, SMO, APOE
9	twinning	24.7	HHIP, SIX3, HCRT, SHH, APOE, APOB
10	craniofacial anomalies	13.8	DHCR7, SHH, PTCH1, FGF8
11	dandy-walker malformation	13.7	ZIC5, ZIC4, ZIC2, ZIC1
12	caudal regression syndrome	13.6	SHH, MNX1
13	nevoid basal cell carcinoma syndrome	13.5	GAS1, SHH, SMO, PTCH1, GLI1
14	anophthalmia/microphthalmia	13.5	SIX6, SIX3, OTX2
15	pituitary gland disease	13.5	PROP1, HESX1, LHX3
16	basal cell carcinoma	13.5	GLI1, GLI2, PTCH1, SMO, SHH
17	stickler syndrome	13.5	SIX3, PRRX1, DHCR7, TGIF1, PTCH1, GLI2
18	empty sella syndrome	13.5	POU1F1, PROP1, LHX3
19	septooptic dysplasia	13.4	POU1F1, PROP1, HESX1, LHX3
20	patau syndrome	13.4	SIX3, DISP1, PTER, ZIC2
21	thyroid hormone resistance syndrome	13.4	POU1F1, PROP1, HESX1, LHX3
22	kallmann syndrome	13.4	PROP1, HESX1, FGF8, LHX3
23	ventricular septal defect	13.4	UBTD2, GLI1, NODAL, GDF1
24	acth deficiency	13.3	TBX19, HESX1, PROP1, POU1F1
25	vacterl association	13.3	SHH, GLI3, GLI2, GLI1
26	isolated growth hormone deficiency	13.3	POU1F1, SOX3, HESX1, OTX2, LHX4
27	triphalangeal thumb-polysyndactyly syndrome	13.3	SHH, MNX1
28	borjeson-forssman-lehmann syndrome	13.2	POU1F1, SOX3, PROP1, HESX1, LHX4, LHX3
29	panhypopituitarism	13.2	POU1F1, SOX3, PROP1, HESX1, LHX4, LHX3
30	hypogonadotropism	13.2	PROP1, HESX1, FGF8, LHX3
31	microcephaly	13.2	SOX3, STIL, DHCR7, TGIF1, SHH, PTER
32	pallister-hall syndrome	13.1	GAS1, GLI1, GLI2, GLI3, PTCH1, SMO
33	combined pituitary hormone deficiency	13.1	LHX4, OTX2, HESX1, PROP1, SOX3, POU1F1
34	pituitary hormone deficiency	13.1	POU1F1, SOX3, PROP1, HESX1, OTX2, LHX4
35	microphthalmia	13.1	SIX6, SIX3, SHH, OTX2, PTER, MNX1
36	cerebellar hypoplasia	13.0	POU1F1, PROP1, HESX1, GLI2, LHX3, BMP4
37	coloboma	13.0	SIX6, SIX3, EAPP, SHH, SNX6, OTX2
38	syndactyly	13.0	EMID2, DHCR7, SHH, PTCH1, GLI3, FGF8
39	anophthalmia	12.9	SIX6, SIX3, POU1F1, SOX3, HESX1, OTX2
40	short stature	12.9	POU1F1, SOX3, PROP1, HESX1, LHX4, LHX3
41	delayed puberty	12.8	NPY, POU1F1, PROP1, HESX1, ESX1, LHX4
42	cleft palate	12.8	DHCR7, SHH, PTER, FGF8, MNX1, BMP4
43	hypopituitarism	12.8	SOX3, POU1F1, SIX3, PROP1, HESX1, LHX3
44	pituitary hypoplasia	12.7	BMP4, LHX3, LHX4, ESX1, OTX2, HESX1
45	pediatric cns embryonal cell carcinoma	12.5	NPY, TDGF1, OTX2, TRAPPC10, GLI2, GLI1
46	pituitary adenoma	12.4	HDAC1, POU1F1, PROP1, HESX1, SHH, TBX19
47	mayer-rokitansky-kuster-hauser syndrome	12.2	DHCR7, TGIF1, PTCH1, TRAPPC10, GLI3, APOB
48	medulloblastoma	12.2	SMO, SHH, TGIF1, DKK1, HHIP, OTX2
49	spina bifida	11.9	SHH, CUBN, PTCH1, APOE, APOB, ZIC4
50	hypothyroidism	11.7	POU1F1, PROP1, HESX1, APOE, APOB, LHX4

Approved drugs:

Drug clinical trials:

MalaCards organs/tissues related to holoprosencephaly:

²²

MGI Mouse Phenotypes related to holoprosencephaly:

²⁵ (show all 22)

id	Description	MGI Source Accession	Score	Top Affiliating Genes
1	taste/olfaction phenotype	MP:0005394	9.7	SIX3, DKK1, HESX1, OTX2, GLI3, CHRD
2	pigmentation phenotype	MP:0001186	8.3	OTX2, TBX19, PTCH1, GLI3, APOE, APOB
3	limbs/digits/tail phenotype	MP:0005371	8.1	SMO, SHH, TWSG1, TGIF1, DKK1, DHCR7
4	hearing/vestibular/ear phenotype	MP:0005377	8.0	NR4A3, SMO, SHH, HESX1, TWSG1, PRRX1
5	muscle phenotype	MP:0005369	7.7	DISP1, OTX2, CTBP1, NODAL, SHH, HCRT
6	normal phenotype	MP:0002873	7.7	NODAL, SHH, HESX1, TGIF1, TGIF2, TDGF1
7	renal/urinary system phenotype	MP:0005367	7.6	CUBN, SHH, TWSG1, DKK1, DHCR7, NPY
8	digestive/alimentary phenotype	MP:0005381	7.1	LRP2, BMP4, CHRD, CDON, MNX1, FOXG1
9	skeleton phenotype	MP:0005390	6.9	NPY, SIM2, SIX3, GAS1, GDF1, PRRX1
10	endocrine/exocrine gland phenotype	MP:0005379	6.8	HESX1, SHH, OTX2, DISP1, TBX19, TWSG1
11	craniofacial phenotype	MP:0005382	6.7	DKK1, ZIC5, ZIC2, BMP4, LRP2, LHX3
12	reproductive system phenotype	MP:0005389	6.5	PTCH1, TBX19, OTX2, SHH, TGIF1, TGIF2
13	vision/eye phenotype	MP:0005391	6.4	GAS1, APOB, FGF8, FOXG1, CDON, CHRD
14	cellular phenotype	MP:0005384	6.3	TWSG1, SHH, SMO, NR4A3, PPP2R3C, TGIF1
15	behavior/neurological phenotype	MP:0005386	6.2	TWSG1, HCRT, SHH, NR4A3, OTX2, PTCH1
16	respiratory system phenotype	MP:0005388	5.9	GDF1, GAS1, HHIP, SIX3, SIM2, NPAS3
17	embryogenesis phenotype	MP:0005380	5.4	GDF1, GAS1, HHIP, HDAC1, SIX3, PRRX1
18	cardiovascular system phenotype	MP:0005385	4.8	BMP4, ESX1, PTCH1, DISP1, OTX2, CUBN
19	homeostasis/metabolism phenotype	MP:0005376	4.2	TGIF1, TWSG1, HCRT, SHH, SMO, NR4A3
20	nervous system phenotype	MP:0003631	3.1	GAS1, HHIP, SIX6, SIX3, SIM2, NPY
21	mortality/aging	MP:0010768	3.0	GLI1, LRP2, BMP4, APOE, APOB, FGF8
22	growth/size phenotype	MP:0005378	2.8	GDF1, GAS1, HHIP, HDAC1, SIM2, NPY

Articles related to holoprosencephaly:

(show top 50)    (show all 106)

id	Title	Authors	Year	Affiliating Genes
1	Mutations in CDON, encoding a hedgehog receptor, result in holoprosencephaly and defective interactions with other hedgehog receptors. (21802063)	Bae G.U.... Krauss R.S.	2011	CDON
2	New findings for phenotype-genotype correlations in a large European series of holoprosencephaly cases. (21940735)	Mercier S.... Odent S.	2011	SHH, ZIC2, TGIF1
3	Genetic counseling and 'molecular' prenatal diagnosis of holoprosencephaly (HPE). (20104616)	Mercier S.... Odent S.	2010	SHH, ZIC2, SIX3
4	Holoprosencephaly and holoprosencephaly-like phenotyp e and GAS1 DNA sequence changes: Report of four Brazilian patients. (20583177)	Ribeiro L.A.... Richieri-Costa A.	2010	GAS1
5	Holoprosencephaly and holoprosencephaly-like phenotyp es: Review of facial and molecular findings in patients from a craniofacial hos pital in Brazil. (20104612)	Richieri-Costa A.... Ribeiro L.A.	2010	SHH, GLI2, SIX3
6	Clinical characterization of individuals with deletio ns of genes in holoprosencephaly pathways by aCGH refines the phenotypic spectr um of HPE. (20066439)	Rosenfeld J.A.... Shaffer L.G.	2010	WIF1
7	Roles of bone morphogenetic protein signaling and its antagonism in holoprosencephaly. (20104603)	Klingensmith J.... Anderson R.M.	2010	CHRD
8	The mutational spectrum of holoprosencephaly-associat ed changes within the SHH gene in humans predicts loss-of-function through eith er key structural alterations of the ligand or its altered synthesis. (19603532)	Roessler E.... Muenke M.	2009	SHH
9	Array-CGH analysis indicates a high prevalence of gen omic rearrangements in holoprosencephaly: an updated map of candidate loci. (19431187)	Bendavid C.... David V.	2009	SHH, ZIC2, SIX3
10	Selective depletion of molecularly defined cortical i nterneurons in human holoprosencephaly with severe striatal hypoplasia. (19234067)	Fertuzinhos S.... Sestan N.	2009	NPY
11	The full spectrum of holoprosencephaly-associated mutations within the ZIC2 gene in humans predicts loss-of-function as the predominant disease mechanism. (19177455)	Roessler E.... Muenke M.	2009	ZIC2
12	EYA4, deleted in a case with middle interhemispheric variant of holoprosencephaly, interacts with SIX3 both physically and functiona lly. (19606496)	Abe Y.... Miyashita T.	2009	SIX3
13	Sonic hedgehog mutations identified in holoprosencephaly patients can act in a dominant negative manner. (19057928)	Singh S.... Robbins D.J.	2009	SHH
14	Sonic hedgehog (SHH) mutation in patients within the spectrum of holoprosencephaly. (19398181)	Bertolacini C.D.... Ribeiro-Bicudo L.A.	2009	SHH
15	Mutations in the human SIX3 gene in holoprosencephaly are loss of function. (18791198)	Domene S.... Feldman B.	2008	SIX3
16	Zebrafish model of holoprosencephaly demonstrates a key role for TGIF in regulating retinoic acid metabolism. (17998248)	Gongal P.A.... Waskiewicz A.J.	2008	TGIF1
17	Haploinsufficiency of Six3 fails to activate Sonic hedgehog expression in the ventral forebrain and causes holoprosencephaly. (18694563)	Geng X.... Oliver G.	2008	SIX3
18	Reduced NODAL signaling strength via mutation of several pathway members including FOXH1 is linked to human heart defects and holoprosencephaly. (18538293)	Roessler E.... Muenke M.	2008	FOXH1, NODAL
19	A mechanism for mutational inactivation of the homeodomain protein TGIF in holoprosencephaly. (17158784)	Ferrand N.... Atfi A.	2007	TGIF1
20	Semilobar holoprosencephaly prenatal diagnosis: an un expected complex rearrangement in a de novo apparently balanced reciprocal tran slocation on karyotype. (17269127)	Kanafani S.... Benzacken B.	2007	SHH
21	Discordant semilobar holoprosencephaly in monozygotic twins with de novo inv dup(15) marker chromosome and de novo mutation on SHH gene. (17556830)	Peng H.H.... Chang S.D.	2007	SHH, ZIC2, SIX3
22	PTCH mutations in four Brazilian patients with holoprosencephaly and in one with holoprosencephaly-like features and normal MRI. (17001668)	Ribeiro L.A.... Richieri-Costa A.	2006	PTCH1
23	Holoprosencephaly: clinical evaluation on audiological and brainstem electrophysiological profiles. (16718676)	Antoneli M.Z.... Richieri-Costa A.	2006	SHH, SIX3
24	First occurrence of aprosencephaly/atelencephaly and holoprosencephaly in a family with a SIX3 gene mutation and phenotype/genotype correlation in our series of SIX3 mutations. (15635066)	Pasquier L.... Encha-Razavi F.	2005	SIX3
25	Targeted disruption of Tgif, the mouse ortholog of a human holoprosencephaly gene, does not result in holoprosencephaly in mice. (15831469)	Shen J.... Walsh C.A.	2005	TGIF1
26	Functional characterization of sonic hedgehog mutations associated with holoprosencephaly. (15292211)	Traiffort E.... Ruat M.	2004	SHH
27	Wide phenotypic variability in families with holoprosencephaly and a sonic hedgehog mutation. (15107988)	Hehr U.... Mueller D.	2004	SHH
28	A novel mutation of the human 7-dehydrocholesterol reductase gene reduces enzyme activity in patients with holoprosencephaly. (15013448)	Shim Y.H.... Paik Y.K.	2004	DHCR7
29	SONIC HEDGEHOG mutations causing human holoprosencephaly impair neural patterning activity. (12709790)	Schell-Apacik C.... Ming J.E.	2003	SHH
30	Previously undescribed nonsense mutation in SHH caused autosomal dominant holoprosencephaly with wide intrafamilial variability. (12567406)	Marini M.... Camera G.	2003	SHH, ZIC2, SIX3
31	Molecular screening of the TGIF gene in holoprosencephaly: identification of two novel mutations. (12522553)	Aguilella C.... David V.	2003	TGIF1
32	Apolipoprotein B and apolipoprotein E genotypes and sporadic holoprosencephaly. (11857554)	Croen L.A.... Lammer E.J.	2002	APOE, APOB
33	Mutations in PATCHED-1, the receptor for SONIC HEDGEHOG, are associated with holoprosencephaly. (11941477)	Ming J.E.... Muenke M.	2002	PTCH1
34	Unusual variant of holoprosencephaly in monosomy 13q. (11910512)	Marcorelles P.... Delezoide A.L.	2002	ZIC2
35	Holoprosencephaly and low molecular weight proteinuria: the human homologue of murine megalin deficiency. (11228189)	Muller D.... Willnow T.E.	2001	LRP2
36	Identification of novel mutations in SHH and ZIC2 in a South American (ECLAMC) population with holoprosencephaly. (11479728)	Orioli I.M.... Muenke M.	2001	SHH, ZIC2, TGIF1
37	Smith-Lemli-Opitz (RHS) syndrome: holoprosencephaly and homozygous IVS8-1G-->C genotype. (11562938)	Nowaczyk M.J.... Porter F.D.	2001	DHCR7
38	The genomic structure, chromosome location, and analysis of the human DKK1 head inducer gene as a candidate for holoprosencephaly. (10965128)	Roessler E.... Muenke M.	2000	DKK1
39	Ectopic expression of telencephalin in brains with holoprosencephaly. (11045672)	Arii N.... Takashima S.	2000	ICAM5
40	The interaction of the carboxyl terminus-binding protein with the Smad corepressor TGIF is disrupted by a holoprosencephaly mutation in TGIF. (10995736)	Melhuish T.A.... Wotton D.	2000	HDAC1, CTBP1, TGIF1
41	Holoprosencephaly, sacral anomalies, and situs ambiguus in an infant with partial monosomy 7q/trisomy 2p and SHH and HLXB9 haploinsufficiency.. (10852374)	Nowaczyk M.J.... Belloni E.	2000	SHH, MNX1
42	Structure of the human lanosterol synthase gene and its analysis as a candidate for holoprosencephaly. (10598817)	Roessler E.... Antonarakis S.E.	1999	LSS
43	Expression of the Sonic hedgehog (SHH) gene during early human development and phenotypic expression of new mutations causing holoprosencephaly. (10441331)	Odent S.... Vekemans M.	1999	SHH
44	Molecular mechanisms of holoprosencephaly. (10527664)	Wallis D.E.... Muenke M.	1999	HHIP
45	Mutations in the homeodomain of the human SIX3 gene cause holoprosencephaly. (10369266)	Wallis D.E.... Muenke M.	1999	SIX3
46	The mutational spectrum of the sonic hedgehog gene in holoprosencephaly: SHH mutations cause a significant proportion of autosomal dominant holoprosencephaly. (10556296)	Nanni L.... Muenke M.	1999	SHH
47	Molecular characterization of breakpoints in patients with holoprosencephaly and definition of the HPE2 critical region 2p21. (8824878)	Schell U.... Muenke M.	1996	SIX3
48	A gene for autosomal dominant sacral agenesis maps to the holoprosencephaly region at 7q36. (7550324)	Lynch S.A.... Strachan T.	1995	MNX1
49	Physical mapping of the holoprosencephaly critical region in 21q22.3, exclusion of SIM2 as a candidate gene for holoprosencephaly, and mapping of SIM2 to a region of chromosome 21 important for Down syndrome. (7485157)	Muenke M.... Fan C.M.	1995	SIM2, HPE1
50	Physical mapping of the holoprosencephaly critical region in 18p11.3. (7485158)	Overhauser J.... Muenke M.	1995	TGIF1

Genes related to holoprosencephaly according to GeneCards:

(show top 50)    (show all 72)

id	Symbol	Description	Score	GeneCards Section Context
1	SIX3	SIX homeobox 3	11.1	Summaries, Publications, Orthologs, Aliases & Descriptions
2	SHH	sonic hedgehog	11.1	Summaries, Publications
3	ZIC2	Zic family member 2	11.1	Summaries, Publications
4	PTCH1	patched 1	11.1	Publications, Summaries
5	TGIF1	TGFB-induced factor homeobox 1	11.1	Publications, Summaries
6	DHCR7	7-dehydrocholesterol reductase	11.1	Summaries, Publications
7	HPE8	holoprosencephaly 8	11.0	Publications, Aliases & Descriptions
8	TRAPPC10	trafficking protein particle complex 10	11.0	Aliases & Descriptions
9	HPE6	holoprosencephaly 6	11.0	Publications, Aliases & Descriptions
10	HPE1	holoprosencephaly 1, alobar	11.0	Publications, Aliases & Descriptions
11	ZIC5	Zic family member 5	11.0	Summaries
12	GLI1	GLI family zinc finger 1	11.0	Summaries
13	GLI2	GLI family zinc finger 2	11.0	Publications
14	ZIC4	Zic family member 4	11.0	Summaries
15	MNX1	motor neuron and pancreas homeobox 1	11.0	Publications
16	ZIC1	Zic family member 1	11.0	Publications
17	FGF8	fibroblast growth factor 8 (androgen-induced)	11.0
18	LRP2	low density lipoprotein receptor-related protein 2	11.0	Publications
19	IGBP1P1	immunoglobulin (CD79A) binding protein 1 pseudogene 1	11.0	Publications
20	BAGE3	B melanoma antigen family, member 3	11.0
21	GAS1	growth arrest-specific 1	11.0	Publications
22	GDF1	growth differentiation factor 1	11.0	Publications
23	ICAM5	intercellular adhesion molecule 5, telencephalin	11.0	Publications
24	NODAL	nodal homolog (mouse)	11.0	Publications
25	TGIF2	TGFB-induced factor homeobox 2	11.0	Publications
26	SIX6	SIX homeobox 6	11.0	Orthologs
27	FOXH1	forkhead box H1	11.0	Publications
28	EAPP	E2F-associated phosphoprotein	11.0	Publications
29	PPP2R3C	protein phosphatase 2, regulatory subunit B'', gamma	11.0	Publications
30	ESX1	ESX homeobox 1	11.0	Disorders
31	FOXG1	forkhead box G1	11.0
32	SIM2	single-minded homolog 2 (Drosophila)	11.0	Publications
33	SOX3	SRY (sex determining region Y)-box 3	11.0
34	LSS	lanosterol synthase (2,3-oxidosqualene-lanosterol cyclase)	11.0	Publications, Functions
35	LHX3	LIM homeobox 3	11.0
36	CHRD	chordin	11.0	Publications
37	HESX1	HESX homeobox 1	11.0
38	CDON	Cdon homolog (mouse)	11.0	Publications
39	TDGF1	teratocarcinoma-derived growth factor 1	11.0
40	DKK1	dickkopf 1 homolog (Xenopus laevis)	11.0	Publications
41	STIL	SCL/TAL1 interrupting locus	11.0	Publications
42	TBX19	T-box 19	11.0
43	TWSG1	twisted gastrulation homolog 1 (Drosophila)	11.0	Disorders, Publications
44	WIF1	WNT inhibitory factor 1	11.0	Publications
45	PWP2	PWP2 periodic tryptophan protein homolog (yeast)	11.0	Disorders
46	HTR5A	5-hydroxytryptamine (serotonin) receptor 5A, G protein-coupled	11.0
47	NR4A3	nuclear receptor subfamily 4, group A, member 3	11.0	Publications
48	LHX4	LIM homeobox 4	11.0
49	OTX2	orthodenticle homeobox 2	11.0
50	PROP1	PROP paired-like homeobox 1	11.0

Pathways related to holoprosencephaly according to GeneDecks:

id	Pathway	Score	Top Affiliating Genes
1	Signaling by NODAL38	10.3	FOXH1, GDF1
2	Development_Hedgehog and PTH signaling pathways in bone and cartilage development41	10.2	SHH, SMO, PTCH1, GLI2, GLI1
3	Development Hedgehog and PTH signaling pathways in bone and cartilage development10	10.1	GLI1, GLI2, PTCH1, SMO, SHH
4	Transcription factors in neurogenesis10	10.1	SIX3, SIM2, SOX3, OTX2, FOXG1, ZIC2
5	Wnt / Hedgehog / Notch3	9.9	WIF1, DKK1, TDGF1, SHH, OTX2, PTCH1
6	Selected targets of Oct-3/410	9.5	BMP4, OTX2, NODAL, DKK1
7	Basal cell carcinoma20	9.3	HHIP, SHH, SMO, PTCH1, GLI3, GLI2
8	SMAD Signaling Network36	9.1	HDAC1, SNX6, CTBP1, FOXH1, BMP4
9	Hedgehog signaling pathway20	8.9	LRP2, GAS1, HHIP, SHH, SMO, PTCH1
10	Pathways in cancer20	8.5	HHIP, HDAC1, SHH, SMO, CTBP1, PTCH1

Compounds related to holoprosencephaly according to GeneDecks:

id	Compound	Score	Top Affiliating Genes
1	sant-242	10.3	SHH, SMO
2	20(s)-hydroxycholesterol42	10.3	SHH, SMO
3	sant-142	10.1	SHH, SMO
4	cyclopamine32	10.0	BMP4, GLI1, PTCH1, SMO, SHH
5	acth32	9.2	TBX19, HCRT, HESX1, PROP1, POU1F1, NPY
6	zinc32 18	9.6	PTCH1, CTBP1, TGIF1, POU1F1, HDAC1, GLI3
7	steroid32	8.3	HDAC1, POU1F1, PROP1, DHCR7, TGIF1, LSS

Cellular components related to holoprosencephaly according to GeneDecks:

id	Name	GO ID	Score	Top Affiliating Genes
1	extracellular space	GO:005615	7.3	NPY, DKK1, TDGF1, TWSG1, SHH, NODAL
2	nucleus	GO:005634	5.4	HDAC1, PPP2R3C, NR4A3, SNX6, SHH, EAPP

Biological processes related to holoprosencephaly according to GeneDecks:

(show top 50)    (show all 55)

id	Name	GO ID	Score	Top Affiliating Genes
1	ventral midline development	GO:007418	10.8	SHH, GLI2, GLI1
2	smoothened signaling pathway involved in regulation of cerebellar granule cell precursor cell proliferation	GO:021938	10.6	SHH, GLI1
3	positive regulation of smoothened signaling pathway	GO:045880	10.6	GAS1, PRRX1, SHH, GLI1
4	somite development	GO:061053	10.6	PTCH1, SMO, SHH
5	regulation of smoothened signaling pathway	GO:008589	10.5	GAS1, OTX2, PTCH1, GLI1, ZIC1
6	ventral spinal cord interneuron specification	GO:021521	10.5	SHH, LHX3
7	embryonic limb morphogenesis	GO:030326	10.5	PRRX1, DKK1, SHH, PTCH1
8	brain development	GO:007420	10.5	SIX3, HESX1, NODAL, PTCH1, FOXG1, ZIC2
9	forebrain morphogenesis	GO:048853	10.4	HESX1, SMO, FGF8
10	embryonic pattern specification	GO:009880	10.4	DISP1, NODAL, SHH, SIM2
11	hindgut morphogenesis	GO:007442	10.4	GLI2, GLI3, SHH
12	dorsal/ventral neural tube patterning	GO:021904	10.4	GAS1, SHH, MNX1, BMP4
13	medial motor column neuron differentiation	GO:021526	10.4	LHX4, LHX3
14	heart looping	GO:001947	10.4	FGF8, SMO, NODAL, SHH, STIL
15	cell fate specification	GO:001708	10.4	SHH, SMO, OTX2
16	mesoderm formation	GO:001707	10.3	DKK1, TWSG1, NR4A3, CHRD
17	organ morphogenesis	GO:009887	10.3	LHX3, LHX4, PTCH1, SOX3, SIX6
18	renal system development	GO:072001	10.3	SHH, SMO, PTCH1, BMP4
19	epidermal cell differentiation	GO:009913	10.3	GLI1, GLI2, HDAC1
20	neural tube closure	GO:001843	10.3	STIL, TGIF1, ZIC5, ZIC2, BMP4
21	lung development	GO:030324	10.3	SIM2, DHCR7, SHH, GLI3, GLI2, GLI1
22	smoothened signaling pathway involved in ventral spinal cord interneuron specification	GO:021775	10.3	GLI3, GLI2
23	positive regulation of protein import into nucleus	GO:042307	10.2	SHH, SMO, GLI3, ZIC1
24	motor axon guidance	GO:008045	10.2	MNX1, LHX4, LHX3
25	hemoglobin import	GO:020028	10.2	CUBN, LRP2
26	response to retinoic acid	GO:032526	10.2	DKK1, SHH, BMP4, LRP2
27	embryonic cranial skeleton morphogenesis	GO:048701	10.2	GAS1, PRRX1, NODAL, BMP4
28	osteoblast differentiation	GO:001649	10.2	GLI2, GLI1, CHRD, BMP4
29	negative regulation of androgen receptor signaling pathway	GO:060766	10.2	HDAC1, NODAL, FOXH1
30	negative regulation of BMP signaling pathway	GO:030514	10.2	DKK1, TWSG1, CHRD, VWC2
31	pituitary gland development	GO:021983	10.1	SOX3, TBX19, GLI2, GLI1, LHX3, BMP4
32	negative regulation of smoothened signaling pathway	GO:045879	10.1	GAS1, HHIP, PTCH1, GLI3
33	BMP signaling pathway	GO:030509	10.1	TDGF1, TWSG1, FGF8, BMP4
34	forebrain development	GO:030900	10.1	STIL, DKK1, TWSG1, SHH, OTX2, FOXG1
35	canonical Wnt receptor signaling pathway	GO:060070	10.0	PROP1, TDGF1, SHH, FGF8
36	proximal/distal pattern formation	GO:009954	10.0	GLI1, GLI2, GLI3
37	branching involved in ureteric bud morphogenesis	GO:001658	10.0	BMP4, FGF8, GLI3, SHH
38	dorsal/ventral pattern formation	GO:009953	9.9	HHIP, PROP1, TGIF1, SHH, OTX2, DISP1
39	palate development	GO:060021	9.8	GAS1, PRRX1, SHH, GLI3
40	embryonic digit morphogenesis	GO:042733	9.6	GAS1, HDAC1, SHH, GLI3, BMP4
41	odontogenesis of dentin-containing tooth	GO:042475	9.6	HDAC1, SHH, GLI3, GLI2, BMP4
42	smoothened signaling pathway	GO:007224	9.2	BMP4, HHIP, STIL, SHH, SMO, DISP1
43	negative regulation of apoptotic process	GO:043066	9.1	GAS1, HDAC1, PROP1, STIL, TDGF1, SHH
44	receptor-mediated endocytosis	GO:006898	9.0	CUBN, APOE, APOB, LRP2
45	post-embryonic development	GO:009791	8.9	DHCR7, APOB, MNX1, BMP4
46	in utero embryonic development	GO:001701	8.8	APOB, GLI3, CUBN, SMO, TDGF1, STIL
47	negative regulation of transcription, DNA-dependent	GO:045892	8.7	HDAC1, SIX3, HESX1, SNX6, CTBP1, ESX1
48	negative regulation of transcription from RNA polymerase II promoter	GO:000122	8.5	TGIF2, DKK1, PROP1, PRRX1, SIM2, HDAC1
49	positive regulation of transcription from RNA polymerase II promoter	GO:045944	8.3	NODAL, SHH, TDGF1, PROP1, POU1F1, SIX3
50	positive regulation of transcription, DNA-dependent	GO:045893	8.1	GLI3, OTX2, SHH, POU1F1, NPAS3, HDAC1

Molecular functions related to holoprosencephaly according to GeneDecks:

id	Name	GO ID	Score	Top Affiliating Genes
1	hedgehog family protein binding	GO:097108	10.2	PTCH1, HHIP
2	growth factor activity	GO:008083	9.6	GDF1, DKK1, TDGF1, NODAL, FGF8, BMP4
3	RNA polymerase II transcription corepressor activity	GO:001106	9.4	CTBP1, SOX3, HDAC1
4	low-density lipoprotein particle receptor binding	GO:050750	9.0	APOB, APOE, DKK1
5	sequence-specific DNA binding	GO:043565	8.5	HESX1, TGIF1, TGIF2, PRRX1, POU1F1, SIX3
6	sequence-specific DNA binding transcription factor activity	GO:003700	7.6	ZIC1, HESX1, TGIF1, TGIF2, PROP1, PRRX1