This document analyzes the gene HOXA1. It maps to chromosome 7p15 and encodes a transcription factor involved in hindbrain development. Mutations cause syndromes like Athabaskan brainstem dysgenesis syndrome that affect hindbrain structures. The gene has 2 transcripts and interacts with proteins like CEBPA and ETS2. It acts in maintenance and generation of hindbrain segments and any mutation could cause syndromes related to the hindbrain.

1. Analysis Report On Gene HoxA1 December 8, 2016
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Submitted to: Dr Nousheen
Submitted by: Hamza Rafique
Roll No: 36870
Topic: Analysis Report on Gene
Semester: 5th
Date: 07-December-2016
Department of Bioinformatics
Hazara University, Mansehra

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Introduction to Gene Homeobox I:
HOXA1 (Homeobox A1) is a Protein Coding gene. Diseases associated with HOXA1
include Athabaskan Brainstem Dysgenesis Syndrome and Hoxa1-Related Disorders. Among
its related pathways are Activated PKN1 stimulates transcription of AR (androgen receptor)
regulated genes KLK2 and KLK3 and Neural Crest Differentiation. It is sequence-specific
transcription factor which is part of a developmental regulatory system that provides cells with
specific positional identities on the anterior-posterior axis. It acts on the anterior body
structures. It act in the maintenance and generation of hindbrain segments[1].
Athabaskan brainstem dysgenesis syndrome (ABDS), Bosley-Salih-Alorainy
syndrome (BSAS), Navajo brainstem syndrome are the main syndromes caused by the
hoxa1[2]. Human HOXA1 syndromes are rare disorders with complex neurological and
systemic symptoms. These syndromes are found among a few American Indian tribes such as
the Navajo and Apaches, who are related to Athabaskan Indians of northern Canada.[3] It is
also found in consanguineous Saudi Arabian and Turkish families. Various names have been
applied (see the synonyms above), but the name human HOXA1 syndromes is generally used
because it is not linked to a specific geographic location.
Methodology:
Gene Annotation:
Map Viewing:
Mapping of gene will be done by the help of Ensemble Database
(http://asia.ensembl.org/) and NCBI (http://www.ncbi.nlm.nih.gov/).
Gene Sequence Retrieval:
Sequence and transcript retrieval will be done with the help of Ensemble.
Exons Retrieval:
Exons of the gene will be retrieved through Ensemble
Protein Annotation:
PBD will be used to retrieve protein structure while domains of protein will be retrieved
through Ensemble.
Domains:
The domain of the protein will be analyzed through Ensemble

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Interactions:
We will use string to obtain the interactions of HOXA1.
Results:
This gene HOXA1 maps on chromosome 7, at 7p15. The Synonyms of Hoxa1 gene are
HOX1, BSAS, HOX1F and found on chromosome 7. This gene has 2 transcripts (splice
variants), 75 orthologues, 12 paralogues, is a member of 1 Ensembl protein family and is
associated with phenotypes. In vertebrates, the genes encoding the class of transcription factors
called homeobox genes are found in clusters named A, B, C, and D on four separate
chromosomes. Expression of these proteins is spatially and temporally regulated during
embryonic development. This gene is part of the A cluster on chromosome 7 and encodes a
DNA-binding transcription factor which may regulate gene expression, morphogenesis, and
differentiation[4]. The encoded protein may be involved in the placement of hindbrain
segments in the proper location along the anterior-posterior axis during development. Two
transcript variants encoding two different isoforms have been found for this gene, with only
one of the isoforms containing the homeodomain region. It has been described as homeobox
protein Hox-A1, homeobox 1F, homeobox A1, lab-like protein, Hox 1.6-like protein,
homeobox protein Hox-1F, HOX A1 homeodomain protein. Hoxa1 interacts with certain other
proteins such as CEBPA, ETS2, PBX1 etc.
Figure 1: Position of HOXA1 on chromosome 7p15

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Fig II & III Shows region view of HOXA1 in detail and the transcript showing Exons
cDNA:
cDNA sequence is shown as below in the figure 4,
Figure IV: cDNA sequence of the transcript HOXA1-001

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Protein Annotation:
The Transcript has total 335 amino acids. Sequence of protein is as follow and 3D structure is
shown in (Fig 6)
MDNARMNSFLEYPILSSGDSGTCSARAYPSDHRITTFQSCAVSANSCGGDDRFLVGRGVQ
IGSPHHHHHHHHRHPQPATYQTSGNLGVSYSHSSCGPSYGSQNFSAPYSPYALNQEADVS
GGYPQCAPAVYSGNLSSPMVQHHHHHQGYAGGAVGSPQYIHHSYGQEHQSLALATYNNSL
SPLHASHQEACRSPASETSSPAQTFDWMKVKRNPPKTGKVGEYGYLGQPNAVRTNFTTKQ
LTELEKEFHFNKYLTRARRVEIAASLQLNETQVKIWFQNRRMKQKKREKEGLLPISPATP
PGNDEKAEESSEKSSSSPCVPSPGSSTSDTLTTSH
Figure V: 3D Structure of the protein
Domains:
Homeodomain and homeobox domain are the consensus domain in the transcript.
Figure VI: Shows Domains of the protein in HOXA1

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Interactions:
Interaction of HOXA1 with other proteins are shown in figure 6,
Figure VII: Interactions ofHOXA1 with other proteins
Variants:
Mostly variants in Hoxa1 are SNPs,there are few insertion and deletions as shown in fig8
Figure VIII: SNP and variants in HOXA1s

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Conclusions:
I concluded that it acts in the maintenance and generation of hindbrain segments. That
is why any mutation in Hoxa1 gene causes different syndromes related to hindbrain segments.
The pathway are Activated PKN1stimulates transcription of AR (androgen receptor) regulated
genes KLK2 and KLK3 and Neural Crest Differentiation
References:
1. Zhang, X., et al., Human growth hormone-regulated HOXA1 is a human mammary epithelial
oncogene. Journal of Biological Chemistry, 2003. 278(9): p. 7580-7590.
2. Tischfield, M.A., et al., Homozygous HOXA1 mutationsdisrupt human brainstem, innerear,
cardiovascular and cognitive development. Nature genetics, 2005. 37(10): p. 1035-1037.
3. Conciatori, M., et al., Association between the HOXA1 A218G polymorphismand increased
head circumference in patients with autism. Biological psychiatry, 2004. 55(4): p. 413-419.
4. McClintock, J., et al., Conserved expression of Hoxa1 in neurons at the ventral
forebrain/midbrain boundary of vertebrates. Development genes and evolution, 2003. 213(8):
p. 399-406.
Links:
I. http://www.genecards.org/cgi-bin/carddisp.pl?gene=HOXA1#summaries
II. https://www.ncbi.nlm.nih.gov/gene/3198
III. http://asia.ensembl.org/Homo_sapiens/Gene/Summary?db=core;g=ENSG0000010599
1;r=7:27092993-27095996;t=ENST00000343060